Basal Insulin Group Research Articles

Real-world impact of adding a glucagon-like peptide-1 receptor agonist compared with basal insulin on metabolic targets in adults living with type 2 diabetes and chronic kidney disease already treated with a sodium-glucose co-transporter-2 inhibitor: The Impact GLP-1 CKD study.

To compare the effectiveness of adding a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with adding basal insulin among adults with type 2 diabetes (T2D) and chronic kidney disease (CKD) already treated with a sodium-glucose co-transporter-2 inhibitor (SGLT2i) and not reaching their glycaemic control targets. A retrospective analysis of the Canadian LMC Diabetes Registry was conducted. Adults who initiated a GLP-1 RA were matched 1:1 to adults who initiated basal insulin in a T2D and CKD population. Changes in metabolic outcomes were evaluated at 26-52 weeks following the therapy start date. Propensity score matching was used to match participants who initiated a GLP-1 RA to participants who initiated basal insulin (n = 153/cohort). A significantly greater reduction in HbA1c at 26-52 weeks of follow-up was observed in the GLP-1 RA cohort compared with the basal insulin cohort (-1.3% ± 1.4% vs. -1.1% ± 1.4%, P = .03). Weight was significantly reduced (-3.4 ± 3.7 vs. 2.6 ± 4.5 kg, P < .001), and the estimated glomerular filtration rate decline slowed significantly (-0.3 ± 8.2 vs. -2.4 ± 10.4 mL/min/1.73m2, P = .02), but the change in albuminuria was not significantly different (-5.7 ± 38.1 vs. -0.5 ± 38.3 mg/mmol, P = .47) at follow-up in the GLP-1 RA group compared with the basal insulin group. No differences in self-reported hypoglycaemic events per week and therapy discontinuations were reported between the cohorts. The study shows the real-world effectiveness of GLP-1 RA therapy for T2D and CKD. GLP-1 RAs provided superior reductions in HbA1c and weight, and greater kidney protection, compared with basal insulin among adults with T2D and CKD already treated with an SGLT2i.

Continuous Insulin Therapy to Prevent Post-Transplant Diabetes Mellitus: A Randomized Controlled Trial

Rationale & ObjectivesHyperglycemia is frequently observed early after transplantation and associated with development of post-transplant diabetes mellitus (PTDM). Here, we assessed continuous subcutaneous insulin infusion (CSII) targeting afternoon hyperglycemia. Study DesignOpen label randomized parallel three-arm design. Settings & ParticipantsN=85 kidney transplant recipients (KTRs) without previous diabetes diagnosis were randomized to postoperative CSII therapy, basal insulin or control. InterventionsInsulin was to be initiated at afternoon capillary blood glucose ≥140 mg/dL (7.8 mmol/L; CSII and basal insulin) or fasting plasma glucose ≥200 mg/dL (11.1 mmol/L; control). OutcomesHbA1c at 3 months post transplant (primary endpoint). PTDM assessed by OGTT at 12 and 24 months. ResultsCSII therapy lasted until median day 18 and maximum day 88. Median HbA1c at month 3 was 5.6% (38 mmol/mol) in the CSII group versus 5.7% (39 mmol/mol) in the control group (p=0.70) and 5.4% (36 mmol/mol) in the basal insulin group (p=0.02). At months 12 and 24, the odds for PTDM were similar compared to the control group (odds ratios [95% confidence intervals], 0.80 [0.18-3.49] and 0.71 [0.15-3.16], respectively) and the basal insulin group 0.96 [0.18-5.68] and 1.51 [0.24-12.84], respectively). Mild hypoglycemia events occurred in the CSII and the basal insulin groups. LimitationsThis study is limited by outdated insulin pump technology, frequent discontinuations of CSII, a complex protocol and concerns regarding reliability of HbA1c measurements. ConclusionsCSII therapy was not superior at reducing HbA1c at month 3 or PTDM prevalence at months 12 and 24 compared to the control or basal insulin group.

#1680 Cardiovascular disease in kidney transplant recipients with post-transplant diabetes mellitus—retrospective analysis from a randomized trial

Abstract Background and Aims Kidney transplant recipients are at risk for glucometabolic deterioration. While many individuals recover their glycemic profiles, some develop posttransplant diabetes mellitus (PTDM). Previous reports have shown that PTDM is associated with increased risk for cardiovascular disease (CVD) and mortality. Here we aimed at assessing the association of PTDM with the development of CVD in kidney transplant recipients from a randomized trial. Method CVD with functioning graft (WFG), all-cause death WFG and death-censored graft loss were retrospectively investigated in N = 263 participants from the Insulin Therapy for the Prevention of New Onset Diabetes after Transplantation multicenter randomized-controlled trial (ITP-NODAT, ClinicalTrials.gov NCT03507829). The clinical trial was conducted from November 2012 through May 2018; kidney transplant recipients without previous diabetes diagnosis had received basal insulin therapy or control for afternoon hyperglycemia. For the current analysis, CVD was defined as a composite of cerebrovascular disease (stroke, transient ischemic attack), coronary artery disease (myocardial infarction, revascularization, stenting), hospitalization for heart failure and vascular/peripheral arterial disease interventions. Participants were to perform three OGTTs at 6, 12 and 24 months posttransplant, which we handled as landmarks in our present analysis. Besides PTDM versus NON-PTDM, we stratified according to basal insulin intervention and control. Cox proportional hazard models were presented unadjusted and adjusted for age, sex and pre-transplant CVD. All patients gave informed consent to participate in the trial and we obtained institutional review board approval for the present analysis. Results Cumulative incidence curves for CVD WFG are presented in Fig. 1. The associated risk of PTDM at 6, 12 and 24 months for CVD WFG tended to be higher in PTDM versus NON-PTDM. At the respective timepoints, the control versus basal insulin groups were similar (Fig. 1). Cause-specific hazard ratios for CVD WFG, all-cause death WFG and death-censored graft loss are presented in Table 1. PTDM was associated with CVD WFG in the univariable models. Corresponding Hazard Ratios (with 95% Confidence Intervals) at 6, 12 and 24 months were 2.53 (1.23, 5.18), 3.19 (1.51, 6.78) and 4.28 (1.94, 9.48), respectively. After adjustment for age, sex and pre-transplant history of CVD, corresponding HRs (95% CIs) were 1.37 (0.64, 2.91), 1.37 (0.61, 3.06) and 3.01 (1.26, 7.22), respectively. PTDM was not associated with all-cause death WFG in the univariable models. Corresponding HRs (95% CIs) at 6, 12 and 24 months were 1.97 (0.82, 4.75), 2.44 (0.95, 6.25) and 2.32 (0.89, 6.05), respectively. PTDM was also not associated with death-censored graft loss in the univariable models. Corresponding HRs (95% CIs) at 6, 12 and 24 months were 1.44 (0.62, 3.36), 2.10 (0.89, 4.94) and 1.15 (0.39, 3.37), respectively. PTDM was neither associated with all-cause death WFG or death-censored graft loss in the adjusted models. Conclusion PTDM diagnosed by OGTT at month 24 was significantly associated with cardiovascular disease independent of age, sex or pre-transplant CVD. The association, however, was not significant when PTDM was diagnosed before month 24. It is possible that transient PTDM diagnosis, early CVD events and study discontinuations before month 24 may have contributed to the differing results over time. Timely PTDM diagnosis may open a window of opportunity for interventions, such as in the form of novel glucose-lowering agents, that may reduce cardiovascular risk in kidney transplant recipients.

Use of iGlarLixi for the Management of Type2 Diabetes in Japanese Clinical Practice: Prior Treatment Subgroup Analysis of the SPARTA Japan Study.

iGlarLixi, a fixed-ratio combination of insulin glargine 100U/mL and the glucagon-like peptide1 receptor agonist (GLP-1 RA) lixisenatide, is one option for treatment intensification in individuals with type2 diabetes (T2D) who are unable to achieve targeted glycaemic control with their current glucose-lowering agent. Real-world data on the impact of prior treatment on the effectiveness and safety of iGlarLixi may be useful to guide individualised treatment decisions. This analysis of the 6-month, retrospective, observational SPARTA Japan study compared glycated haemoglobin (HbA1c), body weight and safety for pre-specified subgroups defined by prior treatment: post oral antidiabetic agent (OAD), GLP-1 RA, basal insulin (BI) + OADs (BOT), GLP-1 RA + BI or multiple daily injections (MDI). The post BOT and MDI subgroups were further divided on the basis of prior dipeptidyl peptidase4 inhibitor (DPP-4i) use, and the post MDI group was divided on the basis of whether participants continued bolus insulin. Of the 432 participants in the full analysis set (FAS), 337 were included in this subgroup analysis. Across subgroups, mean baseline HbA1c ranged from 8.49% to 9.18%. iGlarLixi significantly (p < 0.05) reduced mean HbA1c from baseline in all but the post GLP-1 RA + BI group. At 6months, these significant reductions ranged from 0.47% to 1.27%. Prior DPP-4i exposure had no impact on the HbA1c-lowering effect of iGlarLixi. Mean body weight decreased significantly in the FAS (0.5kg) and the post BOT (1.2kg) and MDI (1.5 and 1.9kg) subgroups but increased in the post GLP-1 RA subgroup (1.3kg). iGlarLixi treatment was generally well tolerated, with very few participants discontinuing because of hypoglycaemia or gastrointestinal events. In participants with suboptimal glycaemic control on various regimens, 6months of iGlarLixi treatment improved HbA1c in all but one prior treatment subgroup (GLP-1 RA + BI), and was generally well tolerated. UMIN-CTR Trials Registry, UMIN000044126; registered 10 May 2021.

Effect of the Concomitant Use of Subcutaneous Basal Insulin and Intravenous Insulin Infusion in the Treatment of Severe Hyperglycemic Patients.

BackgroundNo consensus exists regarding the early use of subcutaneous (SC) basal insulin facilitating the transition from continuous intravenous insulin infusion (CIII) to multiple SC insulin injections in patients with severe hyperglycemia other than diabetic ketoacidosis. This study evaluated the effect of early co-administration of SC basal insulin with CIII on glucose control in patients with severe hyperglycemia.MethodsPatients who received CIII for the management of severe hyperglycemia were divided into two groups: the early basal insulin group (n=86) if they received the first SC basal insulin 0.25 U/kg body weight within 24 hours of CIII initiation and ≥4 hours before discontinuation, and the delayed basal insulin group (n=79) if they were not classified as the early basal insulin group. Rebound hyperglycemia was defined as blood glucose level of >250 mg/dL in 24 hours following CIII discontinuation. Propensity score matching (PSM) methods were additionally employed for adjusting the confounding factors (n=108).ResultsThe rebound hyperglycemia incidence was significantly lower in the early basal insulin group than in the delayed basal insulin group (54.7% vs. 86.1%), despite using PSM methods (51.9%, 85.2%). The length of hospital stay was shorter in the early basal insulin group than in the delayed basal insulin group (8.5 days vs. 9.6 days, P=0.027). The hypoglycemia incidence did not differ between the groups.ConclusionEarly co-administration of basal insulin with CIII prevents rebound hyperglycemia and shorten hospital stay without increasing the hypoglycemic events in patients with severe hyperglycemia.

807-P: Glycemic Control in People with Type 2 Diabetes (PWT2D) Switching from NPH to Insulin Glargine 300 U/mL (Gla-300) : REALI Pooled Database

The effectiveness of Gla-300 in PWT2D switching from NPH is not widely documented. REALI database combines individual data from 14 European studies in T2D. We analyzed data from PWT2D uncontrolled on prior basal insulin (BI) , 1282 switching from NPH and 2899 from other non-NPH BIs (mainly glargine 100 U/mL, 67%) to Gla-300. In the NPH group, mean±SD age was 63±9.4 years, BMI 32.5±5.8 kg/m2, and median diabetes duration 12 years. The majority previously used biguanides (71%) , followed by sulfonylureas (20%) , and dipeptidyl peptidase 4 inhibitors (18%) . HbA1c markedly improved after a 24-week Gla-300 therapy (Figure 1A) . Mean±SD fasting plasma glucose (FPG) decreased from 188.8±55.9 mg/dL at Baseline to 143.3±45.5 at Week 24. Gla-300 was started at a mean dose of 29.4 U/day and titrated up to 35.6 at Week 24, with no body weight (BW) change. In the non-NPH BI group, baseline characteristics were comparable to those in the NPH group, except for higher baseline HbA1c and FPG in the latter. Figure 1B illustrates HbA1c improvement in the non-NPH BI group, at a mean Gla-300 starting dose of 35.4 U/day increasing to 41.7 at Week 24, with no BW change. Hypoglycemia was similarly low in both groups. This analysis shows that PWT2D, previously uncontrolled on BI, benefited from switching to Gla-300 in terms of HbA1c improvement, and this was especially observed in those previously treated with NPH. Disclosure D.Müller-wieland: Advisory Panel; Amarin Corporation, Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Amarin Corporation, Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. N.Freemantle: Consultant; Novo Nordisk, Research Support; Aimmune, ALK-Abelló A/S, Allergan, AstraZeneca, Ipsen Biopharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Sanofi, Vertex Pharmaceuticals Incorporated, Speaker's Bureau; Abbott. R.C.Bonadonna: Advisory Panel; Sanofi, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk. C.Mauquoi: None. G.Bigot: None. M.Bonnemaire: Employee; Sanofi. P.Gourdy: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Mundipharma, Novo Nordisk, Sanofi, Sanofi, Speaker's Bureau; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk. D.Mauricio: Advisory Panel; Merck Sharp &amp; Dohme Corp., Novo Nordisk, Sanofi, Speaker's Bureau; Almirall, S.A., Esteve, Merck Sharp &amp; Dohme Corp., Novo Nordisk, Sanofi. Funding Sanofi

880-P: Insulin Regimen and Glycemic Control in People with Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a progressive disease with many patients requiring insulin treatment. Basal insulin (BI) is often added first followed by escalation to a multiple subcutaneous insulin injection (MSI) regimen. However, many patients with T2DM struggle managing the MSI regimen. As a result, their glycemic control remains poor after starting MSI. Our study investigates whether switching back to BI alone would improve glycemic control. Patients with T2DM and A1C ≥9.0% on MSI regimen seen in our clinic over two years were included in this analysis. Main study outcome was the A1C after ≥3 months of switching back to BI as compared to continuing MSI. We found 24 patients who were switched from MSI to BI and compared them with 58 patients who were continued on MSI (see Table). There were no significant differences at baseline between the two groups. On follow-up, the BI group had a mean change in A1C (%) of -1.6 ± 2.0 compared to -0.7 ± 1.5 in the MSI group. In addition, the daily dose of prescribed insulin on follow-up was lower in the BI group at 46 ± 14 units/day compared to 90 ± 70 units/day in the MSI group. Hypoglycemia rates were also lower in the BI group at 12% compared to 20% in the MSI group. We conclude that simplification of insulin regimen may improve A1C and decrease the risk of hypoglycemia in patients poorly controlled on MSI regimen. The improved glycemic control is likely related to improved adherence and lower risk of errors. Disclosure A. Arunachalam: None. R. Garg: None.

Comparison of adverse effects among different GLP-1 receptor agonists added to basal insulin, and between GLP-1 receptor agonists and basal insulin versus Basal-plus or basal-bolus insulin in type 2 diabetes: A meta-analysis

Diabetes mellitus type 2/ DM2/ - is increasing in incidence in United states and throughout the world mostly due to increasing Obesity epidemy- around 40 % of adult people in USA. Two are the major defects of the disease- insulin resistance which sets up the stage 4-7 years before DM type 2 is diagnosed and relative to the increased resistance insulin deficiency. After the diagnosis of DM type 2 the Insulin resistance stays usually constant while the Insulin deficiency progresses necessitating the intensification of the therapy and eventually the need of Insulin . Initially the insulin is started usually as a basal and eventually as the DM type 2- progresses we add bolus rapid acting insulin to major meal- basal plus regimen/BP/ and eventually to every meal- basal- bolus /BB/ insulin. This intensification of the therapy is frequently able to control DM type 2 , but leads to significant 3-4 kg weight gain with risk of hypoglycemia. Other option of intensification of the therapy of DM type 2 is to add to the oral anti - diabetic medications only basal Insulin and GLP1- RAs. GLP1-RAs decrease post prandial blood sugar as the rapid acting insulin does and the long acting GLP1-RAs also decrease fasting blood sugar. GLP1- RAs suppress the appetite and theoretically might lead to weight loss and less incidence of hypoglycemia compare to BP/BB Insulin regimens, because they act on glucose dependent manner- increase the endogenous insulin production only if the blood sugar is elevated . In our meta- analysis we concentrated our efforts into looking at the side effect of GLP 1- RAs and basal- Insulin combination compare to BP/BB insulin combination like weight loss/gain, incidence of hypoglycemia, adverse events- mainly the gastrointestinal ones. Our secondary end point was the change in HbA1c between GLP1-RAs and basal insulin group compare to BP/BB insulin group in patients with HbA1c 7-11%. This is the first meta- analysis as far as we now comparing those 2- combinations – BB/BP insulin to GLP1-RAs and basal insulin in the terms of looking as a primary end point at the side effects of those combinations.

A Pragmatic Study of Basal and Mid-Mixture Insulins as Starter Insulins in Chinese Patients With Type 2 Diabetes: Observations From Long-Term, Real-World Experience.

IntroductionAccording to Chinese guidelines, basal insulin (BI) or premixed insulins are recommended insulin starters following the failure of oral antihyperglycemic medication (OAM) in Chinese patients with type 2 diabetes (T2D). This pragmatic study investigated the long-term effectiveness, safety, and cost of add-on BI and mid-mixture insulin analog (MMI) regimens in Chinese patients with T2D.MethodsThis multicenter, open-label, pragmatic study randomized patients 1:1 to receive either BI or MMI with OAMs adjusted according to current standards of care. We evaluated the change in glycated hemoglobin (HbA1c) from baseline, safety parameters, and antidiabetic medication costs.ResultsChange in HbA1c from baseline showed a statistically greater decrease at week 48 in the MMI group (MMI: − 2.03% [0.06] vs. BI: − 1.82% [0.06]; P < 0.05). Both groups showed decreases in fasting plasma glucose (mmol/L) (MMI: − 2.53 [0.14] vs. BI: − 3.19 [0.14]; P < 0.01) and postprandial glucose (mmol/L) (MMI: − 4.35 [0.22] vs. BI: − 4.33 [0.23]). More patients in the BI group showed increases in OAM use, while OAM use decreased in the MMI group. Both groups showed stable glycemic control with a very limited insulin dose change from week 24 to week 48. The incidence of total hypoglycemia was higher in the MMI group (MMI: 124% [30.7] vs. BI: 76% [18.5], P < 0.0001), but no incidence of severe hypoglycemia was reported in either group. Treatment costs, in terms of average daily cost and cost of glycemic control, were higher in the BI group.ConclusionIn long-term real-world use, the MMI and BI groups demonstrated improved glycemic control, with the MMI group showing more significant improvement than the BI group. Hypoglycemia incidence was higher in the MMI group, with no major safety issues through week 48. MMI is likely to provide better price value than BI for the treatment of T2D in Chinese patients.Trial RegistrationClinicalTrials.gov identifier: NCT03018938Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01007-z.

Evaluation of Dipeptidyl Peptidase-IV Inhibitor Use in Hospitalized Patients With Diabetes.

Glycemic control within goal blood glucose (BG) ranges is essential to minimize hospital complications for patients with type 2 diabetes mellitus (T2DM). Optimal treatment in the non-intensive care unit (ICU) setting includes a basal insulin containing regimen. Dipeptidyl peptidase-IV (DPP-IV) inhibitors have minimal hypoglycemia incidence and may be an appropriate bolus insulin replacement in the inpatient setting. To determine the effect of basal insulin plus DPP-IV inhibitor compared with basal plus bolus insulin in hospitalized patients with T2DM. This multicenter cohort study included adult patients with T2DM admitted to the non-ICU setting and prescribed either basal insulin plus DPP-IV inhibitor or basal plus bolus insulin. Propensity-score matching was performed for age, sex, Charlson Comorbidity Index, first BG reading during hospitalization, and hemoglobin A1C (A1C). The primary outcome was the difference in mean daily BG during hospitalization. Secondary outcomes included hospital length of stay (LOS), total daily dose (TDD) of insulin, hypoglycemic events, and mean daily BG in patients with an A1C >8%. A total of 105 patients were included in each group. Mean daily BG during hospitalization was lower in the basal insulin plus DPP-IV inhibitor group (199.3 ± 52.5 vs 213.6 ± 45.8 mg/dL; P = 0.04). There was a significant difference in hospital LOS (5 [interquartile range = 3-8] vs 6 [4-11] days; P = 0.02) and short-acting insulin TDD (11.6 ± 9.1 vs 20.5 ± 21.2 units; P < 0.001). No differences were observed in basal insulin TDD and hypoglycemia. There was no difference in mean daily BG in the subgroup analysis of patients with a A1C >8%. A significant difference in mean daily BG and hospital LOS was found with a basal insulin plus DPP-IV inhibitor regimen. Use of a DPP-IV inhibitor to replace bolus insulin in hospitalized patients with T2DM should be considered.

Cardiovascular outcomes and healthcare costs of liraglutide versus basal insulin for type 2 diabetes patients at high cardiovascular risk

We aimed to compare the (1) clinical outcomes including composite cardiovascular outcomes, cardiovascular death, and all-cause death, and (2) healthcare costs of using liraglutide and basal insulin as an initial treatment for patients with type 2 diabetes mellitus (T2DM) and high cardiovascular diseases (CVD) risk. This is a retrospective cohort study using Taiwan’s Health and Welfare Database. A total of 1057 patients treated with liraglutide were identified and matched with 4600 patients treated with basal insulin. The liraglutide group had a lower risk of a composite CVD outcome (hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.50–0.85; p < 0.01), all-cause mortality (HR 0.40; 95% CI 0.28–0.59; p < 0.0001), and nonfatal stroke (HR 0.54; 95% CI 0.34–0.87; p = 0.01). Compared to the basal insulin group, the liraglutide group had lower median per-patient-per-month (PPPM) inpatient, emergency room (ER), and total medical costs, but higher median PPPM outpatient, total pharmacy, and total costs (all p < 0.0001). In conclusion, compared to basal insulin, liraglutide was found to be associated with reduced risk of a composite CVD outcome, nonfatal stroke, and all-cause mortality among high CVD risk patients with T2DM. In addition, liraglutide users had lower inpatient, ER, and total medical costs, but they had higher outpatient and total pharmacy costs.

Comparison of Human Premixed and Basal Plus Short-Acting Insulin Regimens for Individuals With Type 2 Diabetes During Ramadan Fasting.

BackgroundPremixed insulin and basal insulin plus short-acting insulin regimens may be of value for treating individuals with type 2 diabetes (T2DM) who are fasting during Ramadan due to simplicity and better compliance. The objective of this study was to compare the effectiveness of human premixed insulin to basal plus short-acting insulin regimens in the management of fasting individuals with T2DM during Ramadan.MethodsWe conducted a prospective observational study in Basrah (southern Iraq) on 30 individuals with T2DM who fast during Ramadan. The enrolled patients were assigned into two groups at random: one group received a human premixed insulin regimen, the other received a basal plus short-acting insulin regimen. A baseline clinical and biochemical analysis was gathered for all patients at recruitment two weeks before fasting and within four weeks after the end of fasting. Patients were assessed twice during fasting month for insulin dose adjustment and documentation for any hyperglycemia or hypoglycemia.ResultsFourteen patients were assigned to the premixed group, and 16 patients were assigned to the basal plus short-acting insulin group. The mean patient age was 53 ± 8 years, and the mean T2DM duration was 9.3 ± 4.2 years. The two groups were matched by age, body mass index, and glycated hemoglobin (HbA1c). There was no significant difference between the initial and final mean HbA1c in both groups. However, there was more non-significant HbA1c reduction in the premixed group as compared to the basal plus short-acting insulin group. The number of hypoglycemic events and weight changes among the two groups was not significant.ConclusionsBoth human premixed and basal plus short-acting insulin regimens are equally useful for glycemic control for patients with T2DM who choose to fast in observance of the month-long holiday of Ramadan.

2190-PUB: A Pragmatic Study of Basal and Mid-Mixture Insulins as Insulin Starters in Chinese Patients with T2DM

This study aimed to compare the effectiveness and safety of basal insulin (BI) and mid-mixture insulin (MMI) in a real-world setting. Chinese patients with T2DM uncontrolled on oral antihyperglycemic medications (OAMs) were randomized 1:1 to receive add-on BI (QD) or MMI (BID) for 48 weeks (wks). Insulin titration and OAM dose adjustment were based on clinical practice. Compared to BI, MMI led to numerically greater decrease in HbA1c from baseline to wk 24 and statistically greater decrease in HbA1c at wk 48. Fasting blood glucose (FBG) in both groups further decreased from wk 24 to wk 48, and BI caused greater decrease at wk 48 compared to MMI. Both groups had similar decreases in postprandial glucose. Also, significant intergroup difference in OAM use change was detected (p &amp;lt;0.0001) with more patients increasing OAM use in BI group and decreasing OAM use in MMI group. Noticeably, both groups had very limited insulin titration. Body weight increased subtly in both groups. Total hypoglycemia incidence was higher in MMI group through 48 wks, but both groups had low and similar nocturnal hypoglycemia incidence and no severe hypoglycemia. Both BI and MMI could significantly improve glycemic control in Chinese T2DM patients with OAM adjustment and limited insulin titration without major safety issues. Compared to BI, MMI showed larger improvement on glycemic control in relatively long period of treatment. Disclosure L. Chen: Consultant; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S. H. Chen: Employee; Self; Eli Lilly and Company. L. Du: Employee; Self; Eli Lilly and Company. Y. Lou: Employee; Self; Eli Lilly and Company. L. Ji: None.

2198-PUB: The Impact of Basal Insulin Initiation to Background Sulfonylurea Treatment on Hypoglycemia Occurrence: Evaluation of the Balkan Cohort of Dune Study

Background: Optimal glycemic control and proper basal insulin initiation timing when non-insulin treatment becomes insufficient is critical in type 2 diabetes mellitus (T2DM). The DUNE study investigated the effectiveness and safety of newly initiated basal insulin in T2DM patients compared to those who already received insulin. The impact of background therapy with sulfonylureas (SU) on insulin dose and hypoglycemia occurrence was also explored. Methods: The DUNE study was a 12-week, prospective, single-arm, observational study of adults with T2DM. The present sub-analysis included the patients from the Balkan region (Slovenia and Serbia). The first group (n=83) included patients with newly initiated basal insulin and the second group (n=94) included patients who were already treated with basal insulin for up to 12 months. Patients also received other non-insulin antihyperglycemic drugs. Results: The proportion of patients receiving SUs was higher in the group with newly initiated basal insulin (72.3% vs. 55.3%; p&amp;lt;0.001). Basal insulin treatment included NPH or 1st generation basal insulin analogues (BIA) (98.8% vs. 1.2% for newly initiated basal insulin and 83% vs. 17% for already initiated basal insulin), due to local reimbursement policy. Daily insulin doses were lower in newly initiated basal insulin group (11.7±5.58U vs. 18.6±9.18U; p&amp;lt;0.001), the difference remained significant also after 12 weeks of observation (17.5±11.8U vs. 22.6±10.69U; p&amp;lt;0.01). A trend towards higher hypoglycemia occurrence in the newly initiated basal insulin group was observed, despite the lower insulin dose, but with higher percentage of treatment with SUs as a background treatment. Conclusions: Continuation of SUs in T2DM patients, both newly initiated and already initiated with basal insulin therapy (NPH or first-generation insulin analog), should be considered with caution due to the potentially enhanced effect on the risk of hypoglycemia. Disclosure A. Janez: None. M. Lunder: None. M. Janic: None. N. Grulovic: None. D. Zdravkovic: None. A.Z. Jotic: None. K. Lalic: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi. N. Lalic: None.

PDB68 CHARACTERISTICS OF PATIENTS WITH SEVERE HYPOGLYCEMIA AMONG PATIENTS WITH DIABETES USING INSULIN IN COMMERCIALLY INSURED, MEDICARE, AND MEDICAID POPULATION

Severe Hypoglycemia (SH) is an important complication requiring assistance from other persons. This study aimed to describe profiles of patients with SH based on different characteristics. This retrospective study utilized IBM MarketScan Research Database to observe patients experiencing SH between December 2016 and November 2017. A total of 335,766 patients met these following inclusion criteria: presence of diabetes and insulin claims, and continuous enrollment in health plans. Patients with at least one SH were identified using ICD-9-CM/ICD-10-CM codes who were initially treated by emergency medical services or emergency department. Patient characteristics, including age, insurance type, diabetes type, and insulin use, were examined. During the one-year observation period, 9,563 (2.8%) patients with SH were identified with a mean age of 54 years. Of those, 37.7% were Type 1 diabetes (T1D) and 62.3% were Type 2 diabetes (T2D). Overall, the groups that accounted for the largest number of patients with SH were Medicaid adults with T2D using Basal and Bolus (B/B) insulin group (N = 1,638, 17.1%) followed by commercially insured adults with T1D using B/B insulin group (N = 1,488, 15.6%). Among T1D patients with SH (N = 3,602), commercially insured adults using B/B insulin group (41.3%) accounted for the largest proportion. Among T2D patients with SH (N = 5,961), Medicaid adults using B/B insulin group (27.5%) accounted for the largest proportion. Among Medicare patients with SH (N=2,442), T2D patients using B/B insulin group (54.8%) and T2D patients using basal insulin only group (24.8%) made up more than three quarters of the sample. This study reveals characteristics (e.g., Medicaid adults with T2D using B/B insulin; Medicare patients with T2D using basal insulin only) that may benefit from targeted interventions to prevent SH. Continued research is warranted concerning the financial burden of SH and impact of interventions on different patient profile groups.

Clinical outcomes of basal insulin and oral antidiabetic agents as an add-on to dual therapy in patients with type 2 diabetes mellitus

While basal insulin remains the most effective antidiabetic agent and substantially reduces the risk of hypoglycemia, few studies have examined the comparative effect of basal insulin in the real-world setting. This study aimed to assess the outcomes of adding basal insulin compared with thiazolidinediones (TZDs) or dipeptidyl peptidase-4 inhibitors (DPP-4is) as a third antidiabetic agent in patients with type 2 diabetes mellitus (T2DM). A retrospective cohort study involving T2DM was conducted with health administrative data in Taiwan. Patients starting a third antidiabetic agent after receiving a metformin-containing dual combination were identified. The study endpoints included composite major adverse cardiovascular events (MACEs), all-cause mortality, and hypoglycemia. Propensity score matching and Cox modeling were used for analysis. After matching, the basal insulin and TZD groups contained 6,101 and 11,823 patients, respectively, and the basal insulin and DPP-4i groups contained 6,051 and 11,900 patients, respectively. TZDs and DPP-4is were both associated with similar risks of MACEs and hypoglycemia but a lower risk of all-cause mortality than basal insulin (TZDs: HR 0.55, 95% CI 0.38–0.81; DPP-4is: HR 0.56, 95% CI 0.39–0.82). Further studies are needed to elucidate the findings of increased all-cause mortality risk in patients receiving basal insulin, especially those with advanced diabetes.

Dapagliflozin Add-On Therapy Improves Body Composition and Metabolic Parameters in Overweight Type 2 Diabetic Patients: A Pilot Study

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) inhibit renal glucose reabsorption in the proximal tubules, and reduce plasma glucose, body weight and cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). The data on the effect of SGLT-2i on body composition are conflicting: in some reports, they reduce fat mass, while in other reports, they determine reduction of extra- and intra-cellular fluids. The aim of our pilot study was to investigate the body compartments changes and the effects on glycemia and plasma lipids of add-on SGLT2-i dapagliflozin therapy in poorly controlled overweight/obese T2DM patients. Methods: Fifty-six overweight (body mass index (BMI) > 25) uncontrolled (HbA1c > 53 mmol/mol; 7%) T2DM outpatients were recruited. They were treated with metformin and basal insulin (group A) or metformin (group B). Weight, BMI, waist circumference (WC), fasting blood glucose (FPG), HbA1c, plasma lipids, bioelectric parameters and derived body compartments (phase angle (pA), total body water (TBW), fat free mass (FFM) and fat mass (FM)) were assessed at baseline (T0) and after 16 weeks (T1) of dapagliflozin 10 mg add-on treatment. Student’s t -test and one-way analysis of variance (ANOVA) were used to compare the T0 and T1 data. Results: After 16 weeks, all the patients had weight loss (-3.0 ± 0.6 kg, P < 0.0001) and reduced WC (-2.5 ± 0.6 cm, P < 0.0001). Weight reduction was significant in both groups separately (group A: -2.5 ± 0.3 kg, P <= 0.001; group B: -3.4 ± 0.4 kg, P <= 0.001) and was higher in group B. FFM was not impaired in group A (from 60.2 ± 5.2 to 59.5 ± 8.1 kg; ns) and in group B (from 60.4 ± 6.2 to 59.3 ± 6.6 kg; ns). FM decreased in all the patients (29.9 ± 6.84 kg vs. 26.30 ± 7.4 kg, P < 0.000); a higher reduction was found in group B (-3.6 ± 1.2 kg, P < 0.001) vs. group A (-2.3 ± 1.3 kg, P < 0.001). Metabolic control improved in all the patients: FPG 172 ± 49.4 mg/dL vs. 137 ± 36.8 mg/dL at T1, P < 0.0001; HbA1c 69 ± 9.3 mmol/mol (8.5±1.5%) vs. 60 ± 8.7 mmol/mol (7.6±1.4%), P = 0.000. In group A, insulin dose was reduced by 9.3%. Cholesterol and triglycerides (TG) levels decreased in overall population (181.8 ± 48.8 mg/dL vs. 170.7 ± 40.7, P = 0.003; 172 ± 93 mg/dL vs. 143.2 ± 87.8, P = 0.000). Conclusions: Dapagliflozin add-on therapy induced weight loss and metabolic improvement in overweight and obese T2DM patients. Also insulin-treated patients had weight loss (2.5 kg). Bioelectric impedance analysis (BIA) demonstrated FM loss without FFM impairment and was confirmed to be a simple and effective method to assess body composition in clinical practice. J Endocrinol Metab. 2019;9(4):90-94 doi: https://doi.org/10.14740/jem564

Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA) plus Basal Insulin vs. GLP-1RA in Type 2 Diabetes Mellitus—A Systematic Review and Meta-analysis

Combination therapy with Glucagon-like peptide-1 receptor agonist (GLP-1RA) and basal insulin represents a new therapeutic option for diabetes mellitus. We hypothesized that GLP-1RA plus basal insulin is more efficacious, safer and tolerable than GLP-1RA for patients with type 2 diabetes mellitus (T2DM). Randomized controlled trials (RCTs) comparing GLP-1RA plus basal insulin vs. GLP-1RA were searched using PubMed, Cochrane library and www.ClinicalTrials.gov database. Inclusion criteria were: (1) RCTs; (2) comparison between GLP-1RA plus basal insulin vs. GLP-1RA; (3) duration of treatment between 24-30 weeks; and (4) T2DM. Four RCTs with 2,732 participants were included in this meta-analysis. Compared with GLP-1RA alone, GLP-1RA plus basal insulin was associated with a significant reduction in HbA1c (Mean difference [MD]: -0.79%; 95% CI [confidence interval]: -0.96,-0.61; P&amp;lt;0.001) and fasting plasma glucose (FPG) (MD: -2.03mmol/l; 95% CI: -2.28, -1.77; p&amp;lt;0.001). More participants achieved HbA1c ≤7% in the GLP-1RA plus basal insulin group (Odds ratio [OR]: 4.66; 95% CI: 3.00, 7.23; p&amp;lt;0.001). GLP-1RA plus basal insulin was associated with more symptomatic hypoglycaemia (OR: 7.04; 95% CI: 3.81, 13.00; p&amp;lt;0.001) and weight gain (MD: 2.46kg; 95% CI: 2.08, 2.84; P&amp;lt;0.001). There was no significant difference in treatment emergent adverse effects (OR: 0.80; 95% CI: 0.57, 1.11; p=0.18) and discontinuation due to adverse events (OR: 0.52; 95% CI: 0.26, 1.03; p=0.06) between both groups. GLP-1RA plus basal insulin is more efficacious for HbA1c and FPG reduction when compared with GLP-1RA in patients with T2DM. Symptomatic hypoglycaemia and weight gain were more common with GLP-1RA plus basal insulin, but discontinuation due to adverse events was similar between both groups. Disclosure M.M. Satti: None. T. O'Brien: Advisory Panel; Self; Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca. A. Liew: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S.

Achievement of Individualized HbA1c Targets with Self- vs. Physician-Led Titration of Basal Insulin (BI) in People with Type 2 Diabetes (T2DM), Newly or Recently Initiated on BI—Results from the DUNE Real-World Study

DUNE was a 12-week, prospective, observational study of 3139 adults with T2DM, newly (at enrollment) or recently (&amp;lt;12 months) initiated on BI. We evaluated the achievement of individualized HbA1c targets at 12 weeks according to self- vs. physician-led insulin titration. Irrespective of titration method, the proportion of participants who achieved their individualized HbA1c target at week 12 was &amp;lt;30% in both the newly- and recently- initiated BI groups (Table). For both titration groups, there were comparable improvements in fasting plasma glucose from baseline and similar incidence of hypoglycemia. Increase in total daily BI dose for self- vs. physician-led titration in the recently initiated BI group was 4.85 vs. 4.91 U, respectively, while in newly initiated individuals it was 9.68 vs. 7.77 U, respectively. Most participants who were self-titrating did so every 1-3 days, compared with no more frequently than every week for most participants who had physician-led titration. In all groups, the most frequently utilized dose increment was 2 U. The inability of most participants to achieve their target HbA1c in a real-world scenario, irrespective of the method of titration, warrants further investigation. Disclosure L. Berard: Other Relationship; Self; Abbott, Becton, Dickinson and Company, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi, Montmed Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., LifeScan Canada. Consultant; Self; Ascensia Diabetes Care. Other Relationship; Self; Novo Nordisk Inc., Merck &amp; Co., Inc. D. Mauricio: Advisory Panel; Self; AstraZeneca. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Eli Lilly and Company, GlaxoSmithKline plc.. Research Support; Self; GlaxoSmithKline plc.. Advisory Panel; Self; Janssen-Cilag Pty Limited. Speaker's Bureau; Self; Merck Sharp &amp; Dohme Corp.. Board Member; Self; Merck Sharp &amp; Dohme Corp.. Research Support; Self; Merck Sharp &amp; Dohme Corp.. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Sanofi. Board Member; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Sanofi. K. Khunti: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Sanofi-Aventis, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S. Consultant; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Sanofi-Aventis, Takeda Development Centre Europe Ltd., Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis AG, Sanofi-Aventis, Pfizer Inc.. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Sanofi-Aventis, Takeda Development Centre Europe Ltd., Servier. Research Support; Self; Novo Nordisk A/S. Consultant; Self; Pfizer Inc.. Research Support; Self; Novo Nordisk A/S. D.R. Franco: Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Medtronic MiniMed, Inc.. Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi, Eli Lilly and Company. Speaker's Bureau; Self; Abbott. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. C. Candelas: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. V. Pilorget: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. R. Perfetti: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. L. Meneghini: Advisory Panel; Self; Novo Nordisk Inc., Sanofi US. Consultant; Self; Sanofi US, Novo Nordisk Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Other Relationship; Self; American Diabetes Association.

Comparison of peripheral nerve protection between insulin-based glucose control and alpha lipoic acid (ALA) in the streptozotocin (STZ)-induced diabetic rat.

Strict glucose control is a well-proven therapeutic approach for peripheral neuropathies in patients with diabetes. Alpha lipoic acid (ALA) has also been accepted as a therapeutic agent for diabetic peripheral neuropathy (DPN) in the respect of pathogenesis. However, the potential of ALA as a treatment for DPN in comparison to that of glucose control is unclear. In this study, we compared the neuroprotective potential of glucose control and ALA. Animals were divided into 6 groups based on the intervention used, as follows: normal, diabetes (DM), DM+racemic form of ALA, DM+R form of ALA, DM+once daily insulin glargine, and DM+once daily insulin glargine with twice daily insulin glulisine. Various sensory tests were performed after 12 weeks of treatment, and immunohistochemistry of nerve fibers obtained from the sciatic and cutaneous nerves was performed after 24 weeks of treatment. There were no significant differences between the ALA-treated and insulin-treated DM groups in the sensory tests or in antioxidant activity. The axonal diameters and myelin sheath area of the sciatic nerves and the cutaneous small nerves, as assessed based on intraepidermal nerve fiber density, were similar in the ALA-treated and insulin-treated animals, although there was a non-significant trend for a mild increase in the both basal and rapid-acting insulin group compared with non-treated DM group. In conclusion, our results suggest that the neuroprotective benefits of ALA and insulin-based glucose control may be similar, although glucose control may have had slightly more beneficial effects in this animal model of diabetes. Of note, glucose levels should be strictly controlled, including corrections for fluctuations in the glucose level, to obtain therapeutic benefits in DPN.