Mean Change In HbA1c Research Articles

Low-dose empagliflozin as adjunct-to-insulin therapy in type 1 diabetes: A valid modelling and simulation analysis to confirm efficacy.

AimTo confirm the observed reduction in HbA1c for the 2.5 mg dose in EASE‐3 by modelling and simulation analyses.Materials and methodsIndependent of data from EASE‐3 that tested 2.5 mg, we simulated the effect of a 2.5 mg dose through patient‐level, exposure‐response modelling in the EASE‐2 clinical study. A primary semi‐mechanistic model evaluated efficacy considering clinical insulin dose adjustments made after treatment initiation that potentially limited HbA1c reductions. The model was informed by pharmacokinetic, insulin dose, mean daily glucose and HbA1c data, and was verified by comparing the simulations with the observed HbA1c change in EASE‐3. One of two empagliflozin phase 3 trials in type 1 diabetes (EASE‐3 but not EASE‐2) included a lower 2.5 mg dose. A placebo‐corrected HbA1c reduction of 0.28% was demonstrated without the increased risk of diabetic ketoacidosis observed at higher doses (10 mg and 25 mg). Since only one trial included the lower dose, we aimed to confirm the observed reduction in HbA1c for the 2.5 mg dose by modelling and simulation analyses.ResultsThe simulated 26‐week mean HbA1c change was −0.41% without insulin dose adjustment and −0.29% at 26 weeks with insulin dose adjustment. A simplified (descriptive) model excluding insulin dose and mean daily glucose confirmed the –0.29% HbA1c change that would have been observed had the EASE‐2 population received a 2.5 mg dose for 26/52 weeks.ConclusionsThe HbA1c benefit of low‐dose empagliflozin directly observed in the EASE‐3 trial was confirmed by two modelling and simulation approaches.

Effectiveness of Yoga-based Exercise Program Compared to Usual Care, in Improving HbA1c in Individuals with Type 2 Diabetes: A Randomized Control Trial.

Background:This study was designed to evaluate the effectiveness of a yoga-based exercise program (YBEP) in improving glycemic control in people with type 2 diabetes mellitus.Materials and Methods:Patients on stable oral glucose-lowering agents for at least 3 months and HbA1c 7.5%–10% were randomized in 1:1 ratio. The primary outcome measure was the difference of change in mean HbA1c between groups.Results:The participants (n = 81) had mean (±standard deviation) age of 50.6 (±8.5) years and HbA1c of 8.5 ± 0.7% (68.97 ± 7.42 mmol/mol). The follow-up data were available in 96% (78/81) of participants. Of 40 participants, 25 (62.5%) attended ≥75% (≥10 out of 13) of the sessions in YBEP. On the intention to treat analysis, a favorable reduction (0.21% 95% confidence interval [−0.34, 0.75], P = 0.454) in HbA1c was seen in YBEP group as compared to usual care. The reduction in HbA1c by ≥0.5% was observed in 44.7% of participants in YBEP as compared to 37.5% in usual care arm, respectively. Those who attended ≥75% of the sessions had better HbA1c reduction of 0.3% in comparison to 0.1% reduction seen in those who attended <75% of the sessions.Conclusions:YBEP demonstrated a clinically relevant HbA1c reduction compared to usual care in participants who had attended at least 75% of the yoga sessions. The reduction in HbA1c by >0.5% in 44.7% in the yoga group, suggests, that it can be prescribed as an exercise to individuals who are unable to walk either due to limited joint mobility, adverse weather conditions, lack of space for walking, cultural or religious prohibitions for women for outdoor physical activity, and so on.CTRI registration no: CTRI/2017/05/008564.

Long-Term, Real-World Safety and Efficacy of Teneligliptin: A Post-Marketing Surveillance of More Than 10,000 Patients with Type2 Diabetes in Japan.

IntroductionTeneligliptin is a dipeptidyl peptidase 4 inhibitor that was approved for the treatment of type 2 diabetes mellitus (T2DM) in Japan in 2012. We performed a long-term post-marketing surveillance (RUBY) to obtain real-world evidence regarding the safety and efficacy of teneligliptin in Japan.MethodsThis 3-year follow-up RUBY surveillance registered patients with T2DM who started treatment with teneligliptin between May 2013 and February 2015 in Japan. Collected data included demographics, treatments, adverse drug reactions (ADRs) and laboratory variables. Data were evaluated in all patients and in patients divided according to baseline renal function across categories of estimated glomerular filtration rate (G1–G5) and dialysis. Safety was assessed as the incidence of ADRs and efficacy was assessed in terms of glycaemic control, for up to 3 years.ResultsOf 11,677 patients registered, 10,696 and 10,249 were evaluable for safety and efficacy analyses, respectively. The median duration of exposure was 1096 days. ADRs occurred in 412 patients (3.85%) and were serious in 117 patients (1.09%). The most frequent ADR class was gastrointestinal disorders (0.68%), which included constipation. There were no new ADRs warranting attention beyond those already described in teneligliptin’s package insert. ADRs and serious ADRs in renal function subgroups occurred in 3.24–7.14% and 0.65–5.36% in G1–G5, and 4.49% and 1.92% in patients on dialysis, respectively. Reduction in HbA1c was sustained for 3 years after starting teneligliptin (− 0.70% ± 1.36%, p < 0.001 at 3 years). The least-squares mean changes in HbA1c adjusted for baseline were − 0.76% to − 0.66% in G1–G5 at 3 years. Glycated albumin levels decreased in patients on dialysis (− 2.92% ± 4.78% at 3 years).ConclusionThere were no new safety or efficacy concerns about teneligliptin used in long-term, real-world, clinical settings in patients with T2DM with any stages of renal impairment.Trial registrationJapan Pharmaceutical Information Center clinical trials database identifier: Japic CTI-153047.Plain Language SummaryPlain language summary available for this article.Electronic supplementary materialThe online version of this article (10.1007/s12325-019-01189-w) contains supplementary material, which is available to authorized users.

Real-world Effectiveness of Liraglutide vs. Sitagliptin Among Older Patients with Type 2 Diabetes Enrolled in a Medicare Advantage Prescription Drug Plan: A Retrospective Observational Study.

IntroductionLiraglutide and sitagliptin were compared on glycemic control and all-cause healthcare costs over a 1-year period among older adults with type 2 diabetes (65–89 years) enrolled in a national Medicare Advantage Prescription Drug health plan.MethodsThis was a retrospective study in which the index date was the first prescription fill for liraglutide or sitagliptin between 25 January 2010 and 31 December 2014. Post-index treatment persistence and glycosylated hemoglobin (HbA1c) at baseline and 1 year (± 90 days) post-index date were required. Patients were excluded if their record included use of insulin during the baseline period. Inverse probability of treatment weighting using stabilized weights was employed with final covariate adjusted regression modeling to estimate the primary outcome (mean change in HbA1c) and secondary outcomes (achieving glycemic goal and costs), each at 1-year post-index date.ResultsOverall, 3056 patients met the selection criteria, of whom 218 filled prescriptions for liraglutide and 2838 for sitagliptin. Adjusted mean change in HbA1c at 1 year post-index was − 0.42 with liraglutide versus − 0.12 with sitagliptin (P = 0.0012). Adjusted odds of achieving the treatment goals of HbA1c < 7% and achieving an HbA1c reduction of ≥ 1% were higher for those on liraglutide than for those on sitagliptin (1.68, 95% confidence interval [CI] 1.25–2.24 and 1.76, 95% CI 1.31–2.36), respectively. Total healthcare costs in those achieving an HbA1c of < 7% were not significantly different between treatment groups but were higher within the liraglutide group for those achieving an HbA1c < 8%.ConclusionsWhen compared to sitagliptin, liraglutide was associated with greater achievement of an HbA1c < 7% over a 1-year period in an older population. This finding was not associated with a statistically significant increase in all-cause total healthcare costs, although costs were slightly higher in the liraglutide group than in the sitagliptin group.

Impact of a Pharmacist-Led Diabetes Clinic in a Correctional Setting

Incarcerated patients often have a high disease burden and poor access to care in the community. In an effort to ensure glycemic control and appropriate initiation of statin therapy for cardiovascular (CV) risk reduction, a pilot program of pharmacist-led diabetes clinic (PLDC) was implemented in a large inner-city jail. A pre-post study was conducted as a quality improvement initiative. Inclusion criteria were inmate-patients (IPs) diagnosed with type 2 diabetes mellitus, treated with oral antidiabetic medications, managed by PLDC, and with at least 2 glycosylated hemoglobin A1cs (HbA1c). The primary outcome was the change in HbA1c after PLDC. The secondary outcome was the frequency of statin therapy. A total of 240 IPs met the inclusion criteria. Mean HbA1c was 8.2% at baseline and 7.6% at the last follow-up encounter, a change of −0.7% (95% confidence interval [CI]: −0.41% to −0.93%). The most dramatic change was seen in the group with the highest initial HbA1c (HbA1c ≥ 10%), from a mean baseline HbA1c of 11.6% to 8.5%, a change of −3.1% (95% CI: −2.5% to −3.7%). IPs with an initial HbA1c between 7% and 9.9% showed a change in mean HbA1c from 8.4% to 8.0%, a change of −0.4% (95% CI: −0.1% to −0.7%). Of the 240 included IPs, 141 were not on a statin at baseline. The frequency of statin use increased by 50.4% after PLDC. PLDC significantly improved glycemic control and guideline concordance for CV risk reduction. Adding PLDC to multidisciplinary care teams has the potential to improve population health outcomes for this medically complex, yet underserved patient population.

Long-Term Safety and Effectiveness of Linagliptin in Japanese Patients with Type 2 Diabetes Mellitus: A 3-Year Post-Marketing Surveillance Study.

IntroductionClinical trials of linagliptin in Japanese patients conducted to date have had limited observational periods; therefore, there is a need for additional longer-term real-world data. The aim of this study was to investigate the long-term safety and effectiveness of linagliptin in routine clinical practice.MethodsThis was a prospective, observational, post-marketing surveillance study conducted over 156 weeks in patients with type 2 diabetes mellitus who started linagliptin monotherapy. The primary endpoint was the incidence of adverse drug reactions (ADRs). The secondary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to last available observation. Other effectiveness endpoints included the change in HbA1c and change in fasting plasma glucose (FPG) from baseline to week 26 and over the course of the treatment period.ResultsOverall, 2235 and 2054 patients were included in the safety and effectiveness analysis sets, respectively. Patients were mostly male (58.4%), and the mean age was 66.7 years. The incidence of ADRs was 10.7% (n = 240). The most frequent ADRs according to MedDRA preferred terms were diabetes mellitus (n = 35 patients, 1.6%), constipation (n = 21, 0.9%), diabetes mellitus inadequate control (n = 13, 0.6%) and hypertension (n = 13, 0.6%). The mean change in HbA1c from baseline to last observation was − 0.67% [standard deviation (SD) 1.27%, 95% confidence interval − 0.72, − 0.61]. At week 26, HbA1c and FPG showed mean ± SD changes from baseline of – 0.73 ± 1.20% and − 21.02 ± 44.33 mg/dL, respectively, that were sustained until week 156.ConclusionsIn Japanese patients with type 2 diabetes mellitus, linagliptin produced sustained reductions in HbA1c and had a safety profile consistent with the established safety profile of linagliptin.Trial RegistrationClinicalTrials.gov (NCT01650259).Electronic supplementary materialThe online version of this article (10.1007/s13300-019-00723-x) contains supplementary material, which is available to authorized users.

Addressing health disparities in type 1 diabetes through peer mentorship.

Pronounced health disparities exist in type 1 diabetes (T1D) based on socioeconomic status (SES) yet there are a lack of programs designed to promote health equity for vulnerable communities. The All for ONE (Outreach, Networks, and Education) mentoring program was piloted pairing college students and publicly insured teenagers with T1D to assess feasibility as a possible intervention. There were 22 mentors recruited (mean age 20 ± 2 years; 17 [77%] females; mean HbA1c 8.4 ± 1.5%) and matched with mentees based on gender. There were 42 teens randomized to treatment and control groups including 22 teens in the treatment group (age 14 ± 2 years; 17 [77%] females; HbA1c 9.8 ± 2.3%) and 20 teens in the control group (age 14 ± 2 years; 15 [75%] females; HbA1c 8.9 ± 2.0%) followed over 9 months. Outcome measures included HbA1c and the Children's Hope Scale. The intervention included automated text reminders for blood glucose monitoring, text exchanges, social events with education, and clinic visits with mentors/mentees. Mean change in HbA1c for teens was +0.09% in the intervention group, compared with +0.28% in the control group (P = .61); college students had a reduction in HbA1c of -0.22% (P = .38). Treatment group teens had marked improvement in their hope for the future compared to control group teens (P = .04) and were more likely to attend clinic visits (P = .02). This program established feasibility for a model that could be replicated and modified for other types of settings. Additional research is warranted to study the potential long-term benefits of participating in the All for ONE mentoring program.

A National Digital Diabetes Prevention Programme: Feasible, acceptable and effective?

Abstract Background Type 2 Diabetes (T2DM) is a global public health priority affecting 425 million adults with 352 million more at risk of developing T2DM. Intensive group programmes focusing on weight loss and physical activity can prevent or postpone the development of T2DM, but certain groups (e.g working age) find it difficult to attend sessions. Digital options offer a flexible alternative with the potential to widen access and increase uptake. The National Health Service of England (NHSE) has initiated a pilot of a national digital Diabetes Prevention Programme (DPP) to determine its feasibility, acceptability and impact. This is the first national digital DPP in the world, and lessons learnt will be of interest internationally. Methods Single arm, pre-post design located in 9 geographic areas with a total population of 5.6 million adults. Adults identified in primary care as being at risk of T2DM were referred to a digital diabetes prevention intervention (DDPI). Baseline data included demographic details (age, gender, ethnicity, highest level of education achieved) and clinical data (weight (kg), Body Mass Index (BMI) and glycated haemoglobin (HbA1c mmol/mol)). Clinical data were collected at baseline, 6 and 12 months, with the primary outcome change in HbA1c at 12 months. Results The programme was effectively implemented in all 9 areas with a total of 5,053 referrals. 3,228 (64%) of those referred registered with a DDPI. Mean baseline values for registered patients was BMI 31.1, Weight 87.7 kg and HbA1c 43.4 mmol/mol. To date, 2,687 patients have reached the 6 month point, of whom 867 dropped out. Mean (95% CI) HbA1c change was -1.6 (-1.8 to -1.4) mmol/mol (n = 1,264) and mean (95% CI) weight change was -4 (-4.3 to -3.7) kg (n = 1,184). Conclusions A national digital DPP is feasible, acceptable to patients and healthcare providers, and appears to be associated with beneficial impacts on HbA1c and weight in those who participate. Key messages A digital DPP is feasible, acceptable and associated with reductions in weight and HbA1c amongst participants. A digital DPP could be a useful part of a public health strategy to combat T2DM.

The Impact of Flash Glucose Monitoring on Glycaemic Control as Measured by HbA1c: A Meta-analysis of Clinical Trials and Real-World Observational Studies.

IntroductionGlycated haemoglobin A1c (HbA1c) is the established standard measurement for assessment of glycaemic control in people with diabetes. Here we report on a meta-analysis of real-world observational studies on the impact of flash continuous glucose monitoring on glycaemic control as measured by HbA1c.MethodsA total of 271 studies were identified in our search, of which 29 contained data reporting changes in HbA1c over periods from 1 to 24 months that could be used in a statistical analysis. Our meta-analysis focuses on observed change in HbA1c at either 2, 3 or 4 months, in adult or paediatric subjects, as well as a longitudinal analysis up to 12 months in adult subjects. These data were drawn from 25 of the studies identified in our initial search. These reported HbA1c data up to 12 months in a total of 1723 participants with type 1 diabetes (T1D) or type 2 diabetes (T2D) using the FreeStyle Libre® flash glucose monitoring system.ResultsOverall mean change in laboratory HbA1c across study subjects at 2–4 months was − 0.55% (95% CI − 0.70, − 0.39). Amongst the 1023 adults, mean change in HbA1c was − 0.56% (95% CI − 0.76, − 0.36); for the 447 children and adolescents, mean change in HbA1c was − 0.54% (95% CI − 0.84, − 0.23). Based on regression analysis, the degree of change in HbA1c correlated with the initial HbA1c of the study population. A longitudinal analysis in adult subjects (n = 1276) shows that HbA1c fell within the first 2 months and changes were sustained up to 12 months. No significant differences were detected between T1D and T2D.ConclusionThe meta-analysis reported here confirms that starting the FreeStyle Libre system as part of diabetes care results in a significant and sustained reduction in HbA1c for adults and children with T1D and for adults with T2D.FundingAbbott Diabetes Care.

Real-World Clinical Effectiveness and Tolerability of Hydroxychloroquine 400 Mg in Uncontrolled Type 2 Diabetes Subjects who are not Willing to Initiate Insulin Therapy (HYQ-Real-World Study).

The epidemic of T2DM is rising across the globe. Systemic inflammation plays a pivotal role in the pathogenesis and complications of T2DM. Combination of two or more oral hypoglycemic agents (OHA) is widely prescribed in patients with T2DM, however many patients have poor glycemic control despite receiving combination therapy. The new antidiabetic drugs are relatively costly or many patients have anxiety over the use of injectable insulin. The objective of this observational study was to investigate the effectiveness and tolerability of hydroxychloroquine (HCQ) in T2DM patients uncontrolled on multiple OHA and despite high sugar level not willing to initiate insulin therapy in a real-world clinical setting. A prospective, investigator-initiated, observational, single-centred study was conducted where 250 patients (18-65 years) with T2DM for more than 5 years, with uncontrolled glycemia despite on a combination of multiple OHA, HbA1c between ≥7% and <10.5%, FPG >130 mg/dL or PPG >180 mg/dL and BMI between >25 and <39 kg/m2, were prescribed hydroxychloroquine sulphate 400 mg once daily for 48 weeks. Percentage of drugs used at the baseline were as follows: metformin 2000 mg (100%), glimepiride 4 mg (100%), pioglitazone 30 mg (100%), sitagliptin 100 mg (100%), canagliflozin 300 mg (52.4%), empagliflozin 25 mg (22.8%), dapagliflozin 10 mg (17.6%) and voglibose 0.3 mg (62%). Mean change in HbA1c, blood glucose and hs-CRP at baseline, week 12, 24 and 48 were assessed using the paired t-test. After 48 weeks of add-on treatment with HCQ, almost all SGLT-2 inhibitors were withdrawn; metformin dose was reduced to 1000 mg, glimepiride reduced to 1 mg and sitagliptin reduced to 50 mg OD. Patients continued to have good glycemic control. HbA1c was reduced from 8.83% to 6.44%. Reduction in FPG was 40.78% (baseline 177.30 mg/dL) and PPG was reduced by 58.95% (baseline 329.86 mg/dL). Change in mean body weight was -4.66 Kg. The reduction in glycemic parameters and mean body weight was significant (p < 0.0001). Hs-CRP was significantly reduced from 2.70±1.98 mg/L to 0.71±0.30 mg/L 9 (p < 0.0001). More reduction in glycemic parameters and body weight was observed among the patients with higher hs-CRP (> 3 mg/L) as compared to patients with baseline hs- CRP ≤ 3 mg/L. Most common adverse events reported with the drug therapy were GI irritation (3.6%) and hypoglycemia (2%). None of the patients required medical assistance for hypoglycemia. Add-on treatment of HCQ effectively improved glycemic control in T2DM patients uncontrolled on multiple antidiabetic drugs. By virtue of its antidiabetic and anti-inflammatory properties, it may emerge as a valuable therapeutic intervention for the patients with T2DM.

The efficacy and safety of luseogliflozin and sitagliptin depending on the sequence of administration in patients with type 2 diabetes mellitus: a randomized controlled pilot study

ABSTRACTBackground: The efficacy and safety of SGLT-2 and DPP-4 inhibitor monotherapies in T2DM is well established; however, data on the effect of combination therapies and sequence of administration are lacking. We investigated the efficacy and safety of the sequence of SGLT-2 and DPP-4 inhibitor administration in Japanese T2DM patients.Research design and methods: In this single-institution, open-label, randomized controlled study, T2DM patients inadequately controlled (HbA1c ≥6.5%) with conventional therapy were randomized to receive luseogliflozin-sitagliptin (LS; luseogliflozin 2.5 mg for 0–12 weeks, then luseogliflozin plus sitagliptin 50 mg for 12–24 weeks) or sitagliptin-luseogliflozin (SL; sitagliptin 50 mg for 0–12 weeks, then sitagliptin plus luseogliflozin 2.5 mg for 12–24 weeks). The main outcome was the difference in mean change in HbA1c at 24 weeks relative to baseline between both groups.Results: Of the 41 enrolled and randomized patients, 34 completed the study. Mean ± SD HbA1c at baseline was 10.35 ± 1.04% and 10.02 ± 1.40% in the LS and SL groups, respectively, and mean ± SD change in HbA1c at 24 weeks from baseline was −3.81 ± 1.21% vs −2.46 ± 1.42% (P < 0.01), respectively. No drug-related adverse events were reported.Conclusion: Over the 24-week period, LS was more effective in reducing HbA1c levels than SL in Japanese T2DM patients.

Evaluating Glycemic Control in Patients with Type 2 Diabetes Suboptimally Controlled on Basal Insulin: UK ATTAIN Real-World Study.

IntroductionThis retrospective, observational cohort study evaluated the effect of therapy intensification on change in glycated hemoglobin (HbA1c) at 6 and 12 months post intensification in patients with type 2 diabetes (T2D) suboptimally controlled on basal insulin (BI) (i.e., HbA1c ≥ 7.5% [≥ 58 mmol/mol]).MethodsPatients with T2D with suboptimal glycemic control using BI were identified from The Health Improvement Network (THIN) database. Patients who underwent therapy intensification (intensifiers) within 12 months of index 1 (the date of the first incidence of suboptimally controlled HbA1c) were matched (1:1) to patients who did not intensify therapy (non-intensifiers). Index 2 was the date of therapy intensification for intensifiers, or a pseudo date for non-intensifiers that resulted in the same duration from index 1 to index 2 as their matched intensifier patient. Primary outcomes were HbA1c change and proportion of patients achieving the HbA1c target at 6 and 12 months post index 2.ResultsA total of 1342 patients (n = 646 intensifiers; n = 696 non-intensifiers) were included in the analysis. At post index 2, mean HbA1c change was substantially greater at 6 months for intensifiers than for non-intensifiers (− 0.81% vs. − 0.35%), with no additional benefit at 12 months (− 0.81% vs. − 0.49%, respectively). Compared with non-intensifiers, a greater proportion of intensifiers achieved target HbA1c at 6 months (25.1% vs. 18.8%) and at 12 months (33.4% vs. 28.2%).ConclusionsMany real-world patients with T2D suboptimally controlled with BI do not have their therapy intensified. The results of this study suggest that in this patient population, therapy intensification achieves significant reductions in HbA1c at 6 months post intensification, with little additional clinical benefit at 12 months. This suggests that, for patients who fail to achieve their glycemic targets at 6 months, since no meaningful additional clinical benefit is observed at 12 months when continuing the same therapy, further therapy intensification or change should be promptly considered.FundingThis study and the Rapid Service Fees were funded by Sanofi.Trial registration17THIN068.

Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial

Oral semaglutide is the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for glycaemic control in patients with type 2 diabetes. Type 2 diabetes is commonly associated with renal impairment, restricting treatment options. We aimed to investigate the efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment. This randomised, double-blind, phase 3a trial was undertaken at 88 sites in eight countries. Patients aged 18 years and older, with type 2 diabetes, an estimated glomerular filtration rate of 30-59 mL/min per 1·73 m2, and who had been receiving a stable dose of metformin or sulfonylurea, or both, or basal insulin with or without metformin for the past 90 days were eligible. Participants were randomly assigned (1:1) by use of an interactive web-response system, with stratification by glucose-lowering medication and renal function, to receive oral semaglutide (dose escalated to 14 mg once daily) or matching placebo for 26 weeks, in addition to background medication. Participants and site staff were masked to assignment. Two efficacy-related estimands were defined: treatment policy (regardless of treatment discontinuation or rescue medication) and trial product (on treatment without rescue medication) in all participants randomly assigned. Endpoints were change from baseline to week 26 in HbA1c (primary endpoint) and bodyweight (confirmatory secondary endpoint), assessed in all participants with sufficient data. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered on ClinicalTrials.gov, number NCT02827708, and the European Clinical Trials Registry, number EudraCT 2015-005326-19, and is now complete. Between Sept 20, 2016, and Sept 29, 2017, of 721 patients screened, 324 were eligible and randomly assigned to oral semaglutide (n=163) or placebo (n=161). Mean age at baseline was 70 years (SD 8), and 168 (52%) of participants were female. 133 (82%) participants in the oral semaglutide group and 141 (88%) in the placebo group completed 26 weeks on treatment. At 26 weeks, oral semaglutide was superior to placebo in decreasing HbA1c (estimated mean change of -1·0 percentage point (SE 0·1; -11 mmol/mol [SE 0·8]) vs -0·2 percentage points (SE 0·1; -2 mmol/mol [SE 0·8]); estimated treatment difference [ETD]: -0·8 percentage points, 95% CI -1·0 to -0·6; p<0·0001) and bodyweight (estimated mean change of -3·4 kg [SE 0·3] vs -0·9 kg [SE 0·3]; ETD, -2·5, 95% CI -3·2 to -1·8; p<0·0001) by the treatment policy estimand. Significant differences were seen for the trial product estimand: mean change in HbA1c -1·1 percentage points (SE 0·1; -12 mmol/mol [SE 0·8] versus -0·1 percentage points (SE 0·1; -1 mmol/mol [SE 0·8]; ETD -1·0 percentage points, 95% CI -1·2 to -0·8; p<0·0001); mean change in bodyweight -3·7 kg (SE 0·3) versus -1·1 kg (SE 0·3; ETD -2·7 kg, 95% CI -3·5 to -1·9; p<0·0001). More patients taking oral semaglutide than placebo had adverse events (120 [74%] of 163 vs 105 [65%] of 161), and discontinued treatment as a result (24 [15%] vs eight [5%]). Gastrointestinal events, mainly mild-to-moderate nausea, were more common with oral semaglutide than with placebo. Three deaths occurred during the treatment period that were not condsidered to be treatment related, one in the semaglutide group and two in the placebo group. Oral semaglutide was effective in patients with type 2 diabetes and moderate renal impairment, potentially providing a new treatment option for this population. Safety, including renal safety, was consistent with the GLP-1 receptor agonist class. Novo Nordisk A/S.

1140-P: Efficacy and Safety of Evogliptin in Patients with Type 2 Diabetes: A Multicenter, Active-Controlled, Randomized Study with Open Label Extension (EVERGREEN Study)

Background and Aims: Evogliptin is a new dipeptidyl peptidase-4 (DPP-4) inhibitor. We investigated the efficacy and safety of Evogliptin compared with linagliptin in patients with type 2 diabetes (T2D). Materials and Methods: A total of 207 untreated patients with T2D (mean age, 56.1±10.4 years; body mass index, 26.1±3.4 kg/m2) who had HbA1c 7.0-10.0%, prior to the screening were randomized 1:1 for 5 mg Evogliptin (n=102) or 5 mg linagliptin (n=105) once daily for 12 weeks. The primary efficacy endpoint was the change from baseline HbA1c at week 12. The secondary endpoint included the change in mean amplitude of glycemic excursion (MAGE) assessed by 72-hour continuous glucose monitoring. In the extended study for another 12 weeks, open-label treatment with Evogliptin 5 mg qd was conducted in both groups; Evogliptin/Evogliptin group (n=95) and Linagliptin/Evogliptin group (n=92). Results: After 12 weeks of treatment, the mean changes in HbA1c of Evogliptin group and linagliptin group were −0.85% and −0.75%, respectively; the between-group difference was -0.10% (95% confidence interval, −0.32-0.11%), demonstrating non-inferiority, meeting the pre-specified margin of 0.40%. The changes in MAGE were −24.6 mg/dL in the Evogliptin group and −16.7 mg/dL in the linagliptin group, which were significantly lower compared with baseline values in both groups. In the Evogliptin/Evogliptin group at week 24, the mean changes from baseline in HbA1c was −0.94%, achieving HbA1c &amp;lt;7.0% in 80.2% of patients. The incidence and types of adverse events including hypoglycemic events, were comparable between the two groups for 24 weeks. Conclusion: In this study, once-daily evoglipitin 5 mg treatment significantly decreased HbA1c levels by 0.94% at week 24 and improved glycemic variability without any serious adverse events in Korean patients with T2D (ClinicalTrials.gov Identifier: NCT02974504). Disclosure S. Lim: None. G. Kim: None. H. Kwon: None. I. Park: None. K. Ahn: None. C. Park: None. S. Kwon: None. H. Kim: None. S. Park: None. S. Kim: None. M. Moon: None. E. Kim: None. C.H. Chung: None. K. Won: None. K. Park: None. M. Kim: None. D. Chung: None. C. Lee: None. T. Kim: None. M. Lee: None.

99-LB: Meta-analysis of Three Real-World, Chart Review Studies to Determine the Effectiveness of FreeStyle Libre Flash Glucose Monitoring System on HbA1c in Adults with Type 2 Diabetes

Three retrospective chart review studies evaluated the effectiveness of the FreeStyle Libre Flash Glucose Monitoring SystemTM on HbA1c when used by adults with type 2 diabetes (T2DM) as their standard of care in a real-world setting. Each study aimed to determine the effect of FreeStyle Libre when used for between 3 months to 6 months on HbA1c. Each study population included adults on a basal-bolus insulin regimen for at least 1 year who had been using FreeStyle Libre regularly for at least 3 months (either self-funded or prescribed) and with HbA1c between 8.0 and 12.0% (64 to 108 mmol/mol). Pregnant patients were excluded, as were patients on dialysis. This meta-analysis comprised of a total of 363 records from insulin using patients with T2DM from 18 medical centres in Austria, France and Germany. On average, HbA1c was 8.9±0.9% (73.3±9.8 mmol/mol) prior to FreeStyle Libre use, age was 63.5±11.0 years and average duration of insulin use 8.3±5.8 years (mean±SD), 67.8% of patients were on oral antidiabetic medications (metformin, SU, TZD, DPP-4 or SGLT2) and 56.4% were male. CVD, renal and retinopathy complications were reported by 36.4%, 33.9% and 19.6% of patients, respectively. HbA1c results were recorded between 90 and 194 days from the start of use of FreeStyle Libre, between January 2015 and August 2018. Overall mean change in HbA1c, after at least 3 months of using FreeStyle Libre, was significantly reduced by 0.9±0.05% (mean±SE); p&amp;lt;0.0001, with no heterogeneity between countries (Q=0.7, I2=0, p=0.7113). No significant differences were detected between: age group, sex, BMI or duration of insulin use. This meta-analysis of three real-world, chart review studies concludes that people with T2DM on insulin therapy, using FreeStyle Libre for between 3 to 6 months significantly reduced HbA1c. Disclosure J. Kroeger: Board Member; Self; Abbott. Consultant; Self; Abbott. P. Fasching: None. H. Hanaire: Research Support; Self; Abbott, Eli Lilly and Company, LifeScan, Inc., Novo Nordisk A/S. Other Relationship; Self; Eli Lilly and Company, Novo Nordisk A/S.

1189-P: Effectiveness of Hydroxychloroquine (HCQ) 400 mg in Uncontrolled T2D Patients on Dual Therapy of Metformin and Sulfonylurea: A Real-World Experience in India

Objective: Many T2D patients have inadequate glycemic control despite conventional therapy of dual OHAs. Treating such patients in developing countries is a challenge as newer drugs are comparatively costly or patients may have apprehensions for injectable insulin. Objective of this observational study was to evaluate effectiveness of add-on therapy of HCQ in these patients. Methods: A prospective, observational, multi-centre study was conducted where 1,007 T2D patients (age between 18-65 years), uncontrolled on a combination of two OHAs, with HbA1c ≥7.5%, fasting blood glucose of ≥126 mg/dL or 2-hour blood glucose ≥200 mg/dL and body weight ≥60 kg were prescribed hydroxychloroquine sulphate 400 mg once daily for 24 weeks. Mean change in HbA1c, FBG, PPG, serum creatinine and lipid parameters were assessed. Results: At week 24, significant reduction in HbA1c (1.29%), FBG (18%), PPG (23%), TC (9%), LDL-C (12%) and non-HDL-C (12%) was observed (p &amp;lt; 0.0001). At the end of 24 weeks, 36.8% patients achieved HbA1c target of &amp;lt;7%. Conclusion: Hydroxychloroquine effectively improved glycemic and lipid parameters in uncontrolled T2D patients. It may emerge as a valuable therapeutic intervention for patients uncontrolled on two OHAs. Its beneficial effect on lipids may potentially translate to improved CV outcomes. Disclosure I. Purkait: Employee; Self; Ipca Laboratories Ltd. A. Pareek: Employee; Self; Ipca Laboratories Ltd. A. Panneerselvam: None. M.K. Mukhopadhyay: None. S. Kumar: Advisory Panel; Self; Abbott, Alere Inc., Alkem Laboratories, Eli Lilly and Company, Eris Lifesciences, Glenmark Pharmaceuticals Limited, Intas Pharmaceuticals Ltd., Johnson &amp; Johnson, Lupin Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis, Sun Pharma, Torrent Pharma, USV Private Limited, Wockhardt, Zydus Pharmaceuticals, Inc. Consultant; Self; AstraZeneca, Biocon, Boehringer Ingelheim Pharmaceuticals, Inc., Dr. Reddys Laboratories. S.A. Chandratreya: None.

Change in Perceived Stress Moderates the Association Between Weight Change and HbA1c Change in Puerto Rican Women (P21-035-19)

ObjectivesTo assess the association between weight change and change in HbA1c in Puerto Rican men and women, and to evaluate the moderating role of perceived stress in this association MethodsBaseline and 2-year data from the Boston Puerto Rican Health Study were used. Individuals on diabetes medications were excluded. The sample included 218 men and 549 women with complete measures at baseline and 2-year follow up. Stress was assessed with the Perceived Stress Scale-14 and HbA1c from fasting blood samples. Changes in weight, perceived stress, and HbA1c from baseline to year 2 were calculated (i.e., year 2 – baseline). Analyses included linear regression models stratified by sex and adjusted for baseline age, education, smoking status, diet quality, physical activity, body mass index (BMI), baseline HbA1c, diabetes status, menopause status and use of medications for hypertension, hyperlipidemia, depression and thyroid disease. Likelihood ratio (LR) tests were used to evaluate the interaction between weight change and change in perceived stress. ResultsMean baseline to year 2 change in weight was −0.3 kg + 6.1 for women and 0.3 kg + 4.7 for men. Mean change in HbA1c was 0.03% + 0.87 for women and −0.07% + 1.16 for men. Weight change was associated with HbA1c change in women (= 0.037; P < 0.001) but not in men. In women, there was an interaction between weight change and change in perceived stress (p value LR test = 0.005) on change in HbA1c. The coefficient for the interaction was positive and statistically significant (= 0.002; p value = 0.006), indicating that the positive association between weight change on HbA1c change was greater with increasing changes in perceived stress. ConclusionsIn this sample of Puerto Rican men and women, weight change was positively associated with change in HbA1c in women but not in men. Change in perceived stress increased HbA1c sensitivity to weight change. Future studies are needed to replicate our findings and examine pathways that explain this interaction. Funding SourcesResearch was supported by NIH P50 HL105185, P01 AG023394, R01 AG055948, and the University of Massachusetts CCTS (TL1, UL1TR001453). Supporting Tables, Images and/or Graphs▪

1198-P: The M-EASE Studies: A Modeling and Simulation Approach to Further Characterize the Efficacy of Low-Dose Empagliflozin as Adjunctive to Insulin Therapy in Type 1 Diabetes (T1DM)

Among the two phase 3 trials of empagliflozin (EMPA) in T1DM, one (EASE-3), demonstrated diabetic ketoacidosis risk minimization by including a lower dose (2.5 mg) than approved for use in T2DM while maintaining HbA1c benefit of -0.28%. We aimed to determine the effect of HbA1c lowering of EMPA 2.5 mg by modelling and simulation in the phase 3 trial (EASE-2) that did not investigate this dose. The effect of insulin adjustment on HbA1c was also characterized. Independent of empiric data from EASE-3 (that evaluated EMPA 2.5 mg), M-EASE-2, an empirical model, evaluated the direct effect of EMPA exposure on changes in HbA1c after simulated 26- and 52-week treatment durations in the EASE-2 study. M-EASE-2 model development was informed by EASE-2 and EASE-1 (phase 2 study, included EMPA 2.5 mg) data. M-EASE-1, a semi-mechanistic model (informed by EASE-1 and EASE-2 data), simulated changes in HbA1c after a 26-week treatment period (with/without insulin dose adjustment) driven by changes in EMPA exposure, insulin dose and mean daily glucose. Trial simulations were conducted in 239 and 500 patients per dose group in M-EASE-2/-1, respectively. The models were validated using EASE-3 trial data. In M-EASE-2, the simulated mean (median; 95% CI) HbA1c change for EMPA 2.5 mg was -0.29% (-0.29; -0.39, -0.19) at Week 26 and -0.29% (-0.29; -0.40, -0.19) at Week 52. The simulations performed were consistent with EASE-3 results. In M-EASE-1, the 26-week HbA1c change for EMPA 2.5 mg was -0.28% (-0.28; -0.40, -0.09) and -0.41% (-0.40; -0.53, -0.20) with adjusted and stable insulin therapy, respectively. The HbA1c benefit from low-dose EMPA 2.5 mg that was directly observed in a phase 3 clinical trial was confirmed using two modelling approaches from independent studies. Efficacy was sustained over 52 weeks, and the approach predicted that greater efficacy of EMPA as adjunct to insulin in T1DM can be achieved on a stable vs. variable insulin dose. Disclosure B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi. N. Soleymanlou: Employee; Self; Boehringer Ingelheim Canada Ltd. J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Melior Pharmaceuticals, Inc., Bukwang Pharm. Co., Ltd., Merck &amp; Co., Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc. Other Relationship; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. J.S. Skyler: Advisory Panel; Self; ADOCIA, Applied Therapeutics, Dance Biopharm Holdings Inc., Orgenesis Ltd., Tolerion, Inc., Viacyte, Inc. Board Member; Self; Dexcom, Inc., Intarcia Therapeutics, Inc., Moerae Matrix, Inc. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Dalcor, Dialogics, Elcelyx Therapeutics, Inc., Esperion, GeNeuro Innovation, Ideal Life, Immunomolecular Therapeutics, Intrexon, Kamada, Nestlé, Sanofi, Valeritas, Inc., Zafgen, Inc. Stock/Shareholder; Self; Dexcom, Inc., Ideal Life, Intarcia Therapeutics, Inc., Intrexon, Moerae Matrix, Inc. L.M. Laffel: Advisory Panel; Self; Lilly Diabetes, Novo Nordisk A/S, Roche Diabetes Care, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Janssen Pharmaceuticals, Inc., UpToDate. K. Liesenfeld: Employee; Self; Boehringer Ingelheim International GmbH. D. Neubacher: Employee; Self; Boehringer Ingelheim Pharma GmbH &amp; Co. KG. M. Riggs: Consultant; Self; Boehringer Ingelheim International GmbH. C.K. Johnston: Consultant; Self; Boehringer Ingelheim International GmbH. R.J. Eudy-Byrne: Consultant; Self; Boehringer Ingelheim International GmbH. Other Relationship; Spouse/Partner; Eli Lilly and Company, Medtronic, Tandem Diabetes Care. A. Elmokadem: None. J. George: Employee; Self; Boehringer Ingelheim International GmbH. J. Marquard: Employee; Self; Boehringer Ingelheim International GmbH. V.C. Nock: Employee; Self; Boehringer Ingelheim Pharma GmbH &amp; Co. KG. Funding Boehringer Ingelheim; Eli Lilly and Company

636-P: Effect of Obesity and Weight Variations on the Decline of Ankle-Brachial Index in Type 2 Diabetes Subjects without Peripheral Artery Disease

Object: There are very few studies that evaluate the influence of obesity and weight variations on change in ankle-brachial index (ABI) in subjects with type 2 diabetes (T2D) but without peripheral artery disease (PAD). Methods: In this case-control study, T2D subjects who were without baseline PAD (0.9 ≤ ABI &amp;lt; 1.4), and received minimum 2-year interval ABI exams were included. Subjects with prior diagnosed or treated PAD were excluded. Baseline body mass index (BMI) of all subjects was categorized as normal weight (&amp;lt; 23 kg/m2), overweight (23∼25 kg/m2), and obesity (≥ 25 kg/m2). Weight changes during follow-up were categorized by the percentage of weight change; weight loss (&amp;lt; -3%), stable (-3∼3%), gain (&amp;gt; 3%). Subjects with ABI decline were defined as one or both legs worsened to the abnormal (ABI &amp;lt; 0.9) at follow-up exam. Results: A total of 575 subjects were analyzed (188 normal, 140 overweight, and 245 obesity). During the median 2.9 years of follow-up period, 122 (21.2%) subjects showed ABI decline. When split by category of BMI and weight change, the incidence rate of ABI decline showed stepwise increasing pattern according to the obesity and weight gain. Multivariable logistic regression analysis showed that baseline obesity (vs. normal) was significantly associated with the risk of developing ABI decline after adjusting for age, sex, smoking, diabetes duration, mean HbA1c, GFR, LDL cholesterol, blood pressure, hypertensive medication, insulin use, statin use, antiplatelet use, and weight change (OR = 2.06, 95% CI = 1.22 - 3.49). On the contrary, weight loss was significantly associated with reduction in risk of developing ABI decline (OR = 0.52, 95% CI = 0.31 - 0.86). Conclusion: Obesity is an independent risk factor for developing ABI decline in T2D subjects without PAD, whereas weight loss is an independent protective factor. Weight loss should be emphasized especially in obese subjects with T2D. Disclosure Y. Yang: None. J. Lim: None. E. Lee: None. K. Yoon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc. Speaker's Bureau; Self; Takeda Pharmaceutical Company Limited. B. Cha: None. S. Lee: None. Y. Cho: None.

1276-P: Effect of Trial Participation on Metabolic Parameters in People with Progressive Diabetic Complications

Multiple randomized controlled trials (RCTs) in people with diabetes have demonstrated a substantial placebo effect, as a result of enhanced patient-physician interaction time. In RCTs focused on glycemic control, the non-pharmacological component of clinical inertia was independent of age and presence of microvascular complications. Here we explore if trial participation per se improves metabolic parameters in people with diabetic complications, independent of trial focus. Participants from a clinical development program focusing on progression of diabetic macular edema (DME) randomized to receive either a sham intravitreal injections or laser therapy were pooled. The primary 12-month outcomes were changes in retinal parameters while for this analysis we assessed the least square (LS) mean change in metabolic parameters, HbA1c and fasting plasma glucose (FPG). Participants were stratified by age (&amp;lt;70/≥70 years) and change in eGFR (an internal standard for monitoring disease progression). Participants (n=288, 46% women) had a mean±SD age of 62.9±9.2 years, diabetes and DME durations 12.6±9.0 and 1.5±2.2 years, respectively. The baseline HbA1c was well controlled, 7.4±1.1% and FPG was 8.9±3.3 mmol/l. The mean eGFR was 84.1±25.1 ml/min/1.73m2 and most subjects were at a normotensive target of mean BP 137/78 mmHg. At 12 months, the LS mean HbA1c change ±SEM from baseline was 0.1±0.1 and FPG 0.5±0.2 mmol/l. While no difference was seen between the age groups for HbA1c (0.1% for both), FPG reduction was numerically higher in elderly (0.8 vs. 0.4 mmol/l). The mean decline in eGFR was −6.5±0.8 ml/min/1.73m2 in both age groups. Trial participation per se does not improve metabolic parameters of people with diabetes, where the trial focus is not on metabolic control. This implies providing unfocused time for people with diabetes will not improve metabolic control, suggesting focused consultations between people with diabetes and healthcare providers for management of diabetes. Disclosure P.M. Paldánius: Employee; Self; Novartis AG. Stock/Shareholder; Self; Novartis AG. W.D. Strain: Research Support; Self; Bayer AG, Takeda Development Centre Europe Ltd. Speaker's Bureau; Self; NAPP Pharmaceuticals Limited, Novartis AG, Novo Nordisk A/S. Funding Novartis AG