Absolute Reduction In HbA1c Research Articles

The role of treatment of hepatitis C with direct-acting antiviral agents on glycaemic control in diabetic patients: An updated systematic review and meta-analysis.

Recent studies suggested that successful clearance of chronic Hepatitis C Virus (HCV) by using direct-acting antiviral (DAA) agents could improve glycemic control in patients with diabetes; however, some studies failed to identify this benefit. We conducted a systematic review and meta-analysis to assess the impact of sustained virologic response (SVR) after treatment with DAA agents on glycemic control. Embase, Scopus and PubMed were searched through March 26th, 2023, for all studies evaluating whether eradication of HCV infection with DAAs is associated with an impact on glycemic control. Only studies with data on glycemic control, including haemoglobin A1c (HbA1c), fasting glucose, or Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), at least 12-week post-SVR were included. Sixteen studies met our eligibility criteria and were included in qualitative analysis. The mean HbA1c was 8.05% (95% CI: 7.79%-8.31%) before treatment and 7.19% (95% CI: 6.98%-7.39%) after treatment. There was a significant mean absolute reduction in HbA1c of 0.72% (95% CI: 0.52%-0.93%) with high heterogeneity between studies (I2 = 91.7%). The reduction in HbA1c remained significant in the subgroup analysis at 3 months follow up post SVR [0.74% (95% CI: 0.57%-0.91%)] and at least 6 months follow up [0.66% (95% CI: 0.23%-1.10%)]. We found a significant reduction in HbA1C after SVR in patients with type 2 diabetes mellitus, reflecting better glycemic control with HCV eradication. This data highlights an important extrahepatic benefit of HCV eradication.

Glucagon-like peptide-1 analogues in monogenic syndromic obesity: Real-world data from a large cohort of Alström syndrome patients.

To examine the real-world efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in monogenic obesity in patients with Alström syndrome (ALMS). We screened 72 UK adult patients with ALMS and offered treatment to 34 patients meeting one of the following criteria: body mass index of 25 kg/m2 or higher, insulin resistance, suboptimal glycaemic control on antihyperglycaemic medications or non-alcoholic fatty liver disease. In total, 30 patients, with a mean age of 31 ± 11 years and a male to-female ratio of 2:1, completed 6 months of treatment with GLP-1 RAs either in the form of semaglutide or exenatide. On average, treatment with GLP-1 RAs reduced body weight by 5.4 ± 1.7 (95% confidence interval [CI] 3.6-7) kg and HbA1c by 12 ± 3.3 (95% CI 8.7-15.3) mmol/mol, equating to 6% weight loss (P < .01) and 1.1% absolute reduction in HbA1c (P < .01). Significant improvements were also observed in serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and alanine aminotransferase. The improvement of metabolic variables in our cohort of monogenic syndromic obesity was comparable with data for polygenic obesity, irrespective of weight loss. Data from our centre highlight the non-inferiority of GLP-1 RAs in monogenic syndromic obesity to the available GLP-1 RA-use data in polygenic obesity, therefore, these agents can be considered as a treatment option in patients with ALMS, as well as other forms of monogenic obesity.

474-P: Efficacy of Saroglitazar on Diabetes Dyslipidemia with Higher Triglyceride

Objectives: Diabetes and diabetic dyslipidemia with high triglycerides (TGs) are commonly associated. Saroglitazar is the first dual PPAR α/γ agonist which has been approved in India for diabetes dyslipidemia management. This study aimed at evaluation of the efficacy and long-term safety of Saroglitazar on diabetic dyslipidemia with very high triglyceride (&amp;gt;500 mg/dl) in real-world clinical practice. Methods: This investigation took up the form of a real-world retrospective observational study. In this retrospective study, we identified 150 patients with diabetic dyslipidemia with triglycerides &amp;gt;500 mg/dL at baseline) . They were treated with Saroglitazar once daily. Results: Significant reduction of TG and LDL-cholesterol was observed from baseline to 12th weeks 669.93±81.22 to 268.72±82.32 mg/dl and from 167.68±10. to 118.88±12 mg/dl. This study showed that in addition to statins, Saroglitazar paved the way for significant improvement in all the lipid parameters. At 52 weeks, a reduction in values of TG of 66.9%, LDL-C of 38.47%, total cholesterol of 44.84 %, and non- HDL-C of 52.62 % was evident. Adding Saroglitazar in patients on existing antidiabetic medications had highlighted a crucial 0.8% absolute reduction in HbA1c. Significant amounts of improvements in postprandial plasma glucose and fasting have also been seen. Conclusion: This study concludes that there are no adverse alterations in serum creatinine and edema. Saroglitazar can be considered as an effective therapeutic option in diabetic dyslipidemia with very high triglycerides levels. It is very safe for long-term use. Disclosure A.Sinha: None.

113-LB: Oral Menin Inhibitor, BMF-219, Displays a Significant and Durable Reduction in HbA1c in a Type 2 Diabetes Mellitus Rat Model

Menin is an epigenetic regulatory protein that plays a key role in beta-cell proliferation and function, as previously demonstrated though increased beta-cell mass generation in Men1 knockout mice (Ja et al., 2021;13 (5) :e13524) . Here, we demonstrate the marked potential of an oral menin inhibitor, BMF-219, in durable glycemic control following a short course treatment in a Type 2 Diabetes Mellitus (T2DM) Zucker Diabetic Fatty Rat model. Rats were treated daily with BMF-219, liraglutide or vehicle for 28 days and monitored for an additional 28 days post-treatment. All animals tolerated BMF-219 well throughout the study. Notably, BMF-219 treatment resulted in a significant reduction in HbA1C at Day 21, which reached 3.5% absolute reduction in HbA1C versus vehicle, compared to liraglutide (1.7% reduction) at Day 29 and remained reduced throughout the entire study, including post-treatment. The high-dose arm of BMF-219 showed a strong reduction in 4-hour fasting blood glucose during the treatment up to Day 29. Both BMF-219 dose groups showed improved glycemic control by oral glucose tolerance test (OGTT) on day 25, in contrast to vehicle and liraglutide-treated animals. Additionally, insulin levels, HOMA-IR, HOMA-B, OGTT, HbA1C, and C-peptide levels measured at Day 57 across all groups will be reported. Collectively, these data demonstrate the novel long-acting potential of BMF-219 as an oral treatment for T2DM, in maintaining glycemic control after short-term dosing. Disclosure P. Somanath: Employee; Biomea Fusion, Inc., Stock/Shareholder; Biomea Fusion, Inc. M. Balakrishnan: Employee; Biomea Fusion, Inc., Other Relationship; Gilead Sciences, Inc., Stock/Shareholder; Biomea Fusion, Inc., Gilead Sciences, Inc. T. Butler: Employee; Biomea Fusion Inc. S. Mourya: Employee; Biomea Fusion, Stock/Shareholder; Ascendis Pharma A/S. W. Li: None. T. C. Archer: Employee; Biomea Fusion. B. Law: Stock/Shareholder; Biomea Fusion Inc., Mirum Pharmaceuticals. D. Lu: Employee; Biomea Fusion Inc., Stock/Shareholder; AbbVie Inc. T. Rughwani: None. L. Kumar: None. T. Kinoshita: None.

Treatment of periodontitis for glycaemic control in people with diabetes mellitus.

Glycaemic control is a key component in diabetes mellitus (diabetes) management. Periodontitis is the inflammation and destruction of the underlying supporting tissues of the teeth. Some studies have suggested a bidirectional relationship between glycaemic control and periodontitis. Treatment for periodontitis involves subgingival instrumentation, which is the professional removal of plaque, calculus, and debris from below the gumline using hand or ultrasonic instruments. This is known variously as scaling and root planing, mechanical debridement, or non-surgical periodontal treatment.Subgingival instrumentation is sometimes accompanied by local or systemic antimicrobials, and occasionally by surgical intervention to cut away gum tissue when periodontitis is severe. This review is part one of an update of a review published in 2010 and first updated in 2015, and evaluates periodontal treatment versus no intervention or usual care. OBJECTIVES: To investigate the effects of periodontal treatment on glycaemic control in people with diabetes mellitus and periodontitis. An information specialist searched six bibliographic databases up to 7 September 2021 and additional search methods were used to identify published, unpublished, and ongoing studies. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) of people with type 1 or type 2 diabetes mellitus and a diagnosis of periodontitis that compared subgingival instrumentation (sometimes with surgical treatment or adjunctive antimicrobial therapy or both) to no active intervention or 'usual care' (oral hygiene instruction, education or support interventions, and/or supragingival scaling (also known as PMPR, professional mechanical plaque removal)). To be included, the RCTs had to have lasted at least 3 months and have measured HbA1c (glycated haemoglobin). At least two review authors independently examined the titles and abstracts retrieved by the search, selected the included trials, extracted data from included trials, and assessed included trials for risk of bias. Where necessary and possible, we attempted to contact study authors. Our primary outcome was blood glucose levels measured as glycated (glycosylated) haemoglobin assay (HbA1c), which can be reported as a percentage of total haemoglobin or as millimoles per mole (mmol/mol). Our secondary outcomes included adverse effects, periodontal indices (bleeding on probing, clinical attachment level, gingival index, plaque index, and probing pocket depth), quality of life, cost implications, and diabetic complications. We included 35 studies, which randomised 3249 participants to periodontal treatment or control. All studies used a parallel-RCT design and followed up participants for between 3 and 12 months.The studies focused on people with type 2 diabetes, other than one study that included participants with type 1 or type 2 diabetes. Most studies were mixed in terms of whether metabolic control of participants at baseline was good, fair, or poor. Most studies were carried out in secondary care. We assessed two studies as being at low risk of bias, 14 studies at high risk of bias, and the risk of bias in 19 studies was unclear. We undertook a sensitivity analysis for our primary outcome based on studies at low risk of bias and this supported the main findings. Moderate-certainty evidence from 30 studies (2443 analysed participants) showed an absolute reduction in HbA1c of 0.43% (4.7 mmol/mol) 3 to 4 months after treatment of periodontitis (95% confidence interval (CI) -0.59% to -0.28%; -6.4 mmol/mol to -3.0 mmol/mol). Similarly, after 6 months, we found an absolute reduction in HbA1c of 0.30% (3.3 mmol/mol) (95% CI -0.52% to -0.08%; -5.7 mmol/mol to -0.9 mmol/mol; 12 studies, 1457 participants), and after 12 months, an absolute reduction of 0.50% (5.4 mmol/mol) (95% CI -0.55% to -0.45%; -6.0 mmol/mol to -4.9 mmol/mol; 1 study, 264 participants). Studies that measured adverse effects generally reported that no or only mild harms occurred, and any serious adverse events were similar in intervention and control arms. However, adverse effects of periodontal treatments were not evaluated in most studies. Our 2022 update of this review has doubled the number of included studies and participants, which has led to a change in our conclusions about the primary outcome of glycaemic control and in our level of certainty in this conclusion. We now have moderate-certainty evidence that periodontal treatment using subgingival instrumentation improves glycaemic control in people with both periodontitis and diabetes by a clinically significant amount when compared to no treatment or usual care. Further trials evaluating periodontal treatment versus no treatment/usual care are unlikely to change the overall conclusion reached in this review.

Genome-Wide Meta-analysis Identifies Genetic Variants Associated With Glycemic Response to Sulfonylureas.

OBJECTIVESulfonylureas, the first available drugs for the management of type 2 diabetes, remain widely prescribed today. However, there exists significant variability in glycemic response to treatment. We aimed to establish heritability of sulfonylurea response and identify genetic variants and interacting treatments associated with HbA1c reduction.RESEARCH DESIGN AND METHODSAs an initiative of the Metformin Genetics Plus Consortium (MetGen Plus) and the DIabetes REsearCh on patient straTification (DIRECT) consortium, 5,485 White Europeans with type 2 diabetes treated with sulfonylureas were recruited from six referral centers in Europe and North America. We first estimated heritability using the generalized restricted maximum likelihood approach and then undertook genome-wide association studies of glycemic response to sulfonylureas measured as HbA1c reduction after 12 months of therapy followed by meta-analysis. These results were supported by acute glipizide challenge in humans who were naïve to type 2 diabetes medications, cis expression quantitative trait loci (eQTL), and functional validation in cellular models. Finally, we examined for possible drug-drug-gene interactions.RESULTSAfter establishing that sulfonylurea response is heritable (mean ± SEM 37 ± 11%), we identified two independent loci near the GXYLT1 and SLCO1B1 genes associated with HbA1c reduction at a genome-wide scale (P < 5 × 10−8). The C allele at rs1234032, near GXYLT1, was associated with 0.14% (1.5 mmol/mol), P = 2.39 × 10−8), lower reduction in HbA1c. Similarly, the C allele was associated with higher glucose trough levels (β = 1.61, P = 0.005) in healthy volunteers in the SUGAR-MGH given glipizide (N = 857). In 3,029 human whole blood samples, the C allele is a cis eQTL for increased expression of GXYLT1 (β = 0.21, P = 2.04 × 10−58). The C allele of rs10770791, in an intronic region of SLCO1B1, was associated with 0.11% (1.2 mmol/mol) greater reduction in HbA1c (P = 4.80 × 10−8). In 1,183 human liver samples, the C allele at rs10770791 is a cis eQTL for reduced SLCO1B1 expression (P = 1.61 × 10−7), which, together with functional studies in cells expressing SLCO1B1, supports a key role for hepatic SLCO1B1 (encoding OATP1B1) in regulation of sulfonylurea transport. Further, a significant interaction between statin use and SLCO1B1 genotype was observed (P = 0.001). In statin nonusers, C allele homozygotes at rs10770791 had a large absolute reduction in HbA1c (0.48 ± 0.12% [5.2 ± 1.26 mmol/mol]), equivalent to that associated with initiation of a dipeptidyl peptidase 4 inhibitor.CONCLUSIONSWe have identified clinically important genetic effects at genome-wide levels of significance, and important drug-drug-gene interactions, which include commonly prescribed statins. With increasing availability of genetic data embedded in clinical records these findings will be important in prescribing glucose-lowering drugs.

Cost-effectiveness of financial incentives to improve glycemic control in adults with diabetes: A pilot randomized controlled trial.

PurposeDetermine the cost-effectiveness of three financial incentive structures in obtaining a 1% within group drop in HbA1c among adults with diabetes.Methods60 African Americans with type 2 diabetes were randomized to one of three financial incentive structures and followed for 3-months. Group 1 (low frequency) received a single incentive for absolute HbA1c reduction, Group 2 (moderate frequency) received a two-part incentive for home testing of glucose and absolute HbA1c reduction and Group 3 (high frequency) received a multiple component incentive for home testing, attendance of weekly telephone education classes and absolute HbA1c reduction. The primary clinical outcome was HbA1c reduction within each arm at 3-months. Cost for each arm was calculated based on the cost of the intervention, cost of health care visits during the 3-month time frame, and cost of workdays missed from illness. Incremental cost effectiveness ratios (ICER) were calculated based on achieving a 1% within group drop in HbA1c and were bootstrapped with 1,000 replications.ResultsThe ICER to decrease HbA1c by 1% was $1,100 for all three arms, however, bootstrapped standard errors differed with Group 1 having twice the variation around the ICER coefficient as Groups 2 and 3. ICERs were statistically significant for Groups 2 and 3 (p<0.001) indicating they are cost effective interventions.ConclusionsGiven ICERs of prior diabetes interventions range from $1,000-$4,000, a cost of $1,100 per 1% within group decrease in HbA1c is a promising intervention. Multi-component incentive structures seem to have the least variation in cost-effectiveness.

Genome-Wide Meta-Analysis Identifies the Organic Anion-Transporting Polypeptide Gene &lt;i&gt;SLCO1B1&lt;/i&gt; and Statins as Modifiers of Glycemic Response to Sulfonylureas

Background: Sulfonylureas, the first available drugs for the management of type 2 diabetes, remain widely prescribed today. However there exists significant variability in glycaemic response to treatment. We aimed to establish heritability of sulfonylurea response and identify genetic variants and interacting treatments associated with HbA1c reduction. Methods: As an initiative of the Metformin Genetics Plus (MetGen Plus) and the DIabetes REsearCh on patient straTification (DIRECT) consortia, 5,485 white European adults with type 2 diabetes treated with sulfonylurea were recruited from 6 referral centres in Europe and North America. We first estimated heritability using generalized restricted maximum likelihood (REML) and then undertook GWAS of glycemic response to sulfonylureas measured as HbA1c reduction after 12 months of therapy in each cohort using linear regression followed by meta-analysis. These results were supported by cis-eQTLs and functional validation in cellular models. Findings: After establishing that sulfonylurea response is heritable (37±11%), we identified two independent loci near the GXYLT1 and SLCO1B1 genes associated with HbA1c reduction. The C-allele at rs1234032, near GXYLT1, was associated with 0.14% (1.5 mmol/mol), p=2.4×10−8) lower HbA1c reduction. Similarly, the C-allele was associated with higher glucose trough levels (β=1.61, p=0.005) in healthy volunteers in the SUGAR-MGH given glipizide (N = 857). The C-allele of rs10770791, near SLCO1B1, was associated with 0.11% (1.2 mmol/mol) greater HbA1c reduction (p=4.8×10 −8 ). In 1,183 human liver samples, the C-allele at rs10770791 is a cis-eQTL for reduced SLCO1B1 expression (p=1.61×10−7) which, together with functional studies in cells expressing SLCO1B1, supports a key role for hepatic SLCO1B1 (encoding OATP1B1) in regulation of sulfonylurea transport. Further, a significant interaction between statin use, sulfonylurea response and SCLO1B1 genotype was observed (p=0.001). In statin non-users (but not users), C-allele homozygotes at rs10770791 had a large absolute reduction in HbA1c (0.48±0.12% (5.2±1.26 mmol/mol)), equivalent to initiating a DPP4 inhibitor. Interpretation: We have identified clinically important genetic effects at genomewide levels of significance, and important drug-drug-gene interactions, which include commonly prescribed statins. With increasing availability of genetic data embedded in clinical records these findings will be important when prescribing glucose-lowering drugs. Funding Statement: Innovative Medicines Initiative, the National Institutes of Health, the Geisinger Health Plan Quality Pilot Fund. Declaration of Interests: ERP has received honoraria for speaking from Lilly and Sanofi. JCF has received honoraria for speaking at scientific conferences from Novo, and for consulting from Goldfinch Bio. All other authors declare no competing interest. Ethics Approval Statement: This study was approved by respective research ethics review boards and participants provided written informed consent.

Analysis of the effectiveness of second oral glucose-lowering therapy in routine clinical practice from the mediterranean area: A retrospective cohort study

AimTo compare the changes in HbA1c, the effect on body weight or both combined after the addition of a DPP-4i, SGLT-2i, or sulfonylureas (SU) to metformin in real-world condition. MethodsWe used a primary care SIDIAP database. The included subjects were matched by propensity score according to baseline age, sex, HbA1c, weight, inclusion date, diabetes duration, and kidney function. ResultsMean absolute HbA1c reduction was: 1.28% for DPP4i, 1.29% for SGLT2i and 1.26% for SU. Mean weight reduction was: 1.21 kg for DPP4i, 3.47 kg for SGLT2i and 0.04 kg for SU. The proportion of patients who achieved combined target HbA1c (≥0.5%) and weight (≥3%) reductions after the addition of DPP-4i, SGLT-2i or SU, was: 24.2%, 41.3%, and 15.2%, respectively. Small differences in systolic blood pressure reduction (1.07, 3.10 and 0.96 mmHg, respectively) were observed in favour of SGLT-2i. Concerning the lipids, we observed small differences, with an HDL-cholesterol increase with SGLT-2i. ConclusionOur real-world study showed that the addition of SGLT-2i to metformin was associated with greater reductions in weight and the combination target of weight-HbA1c compared to SU and DPP4 inhibitors. However, similar hypoglycaemic effectiveness was observed among the three-drug classes.

Glycemic and cardiometabolic effects of exercise in South Asian Sri Lankans with type 2 diabetes mellitus: A randomized controlled trial Sri Lanka diabetes aerobic and resistance training study (SL-DARTS)

Background and aimsTo examine the effects of aerobic training (AT) and resistance training (RT) compared to standard care on glycemic control in South Asian Sri Lankan adults with Type 2 Diabetes Mellitus (T2DM). MethodsRandomized controlled trial (RCT) with parallel-group design recruited 86 sedentary Sri Lankans (aged 35–65 years) with T2DM into aerobic training (AT, n = 28), resistance training (RT, n = 28) and control (CN, n = 30) groups. Supervised progressive exercise training consisting of 75 min per session, 2 days per week for 12 weeks was conducted. The primary outcome was pre- and post-intervention absolute change in hemoglobin A1c (HBA1c). Secondary outcomes were serum lipids, liver enzymes, chronic inflammatory status, anthropometry, body composition and blood pressure. ResultsThe absolute change in HbA1c of RT vs. CN was −0.08% (95% CI, 0.8% to −0.7%, p = 0.8) and AT vs. CN was −0.22% (95% CI, 0.95% to −0.5%). Subgroup analysis (n = 49) with a high baseline HbA1c (>7.5%), absolute reduction in HbA1c in exercise groups were statistically significant (RT vs. CN was −0.37%; 95% CI 1.3% to −0.6%, p = 0.04 and AT vs. CN was −0.57%; 95% CI 1.7% to −0.6%, p = 0.03). The effect sizes (total and subgroup HbA1c >7.5%) ranged from 0.7 to 1.0 in AT, 0.4 to 1.1 in RT compared to 0.35 to 0.6 for the CN. Secondary outcomes did not significantly differ among groups. ConclusionsExercise training 2 days/week improved glycemic control in Sri Lankan adults with T2DM and the effects were significant in high baseline HbA1c (>7.5%) groups (RT > AT).

Glycemic Control after Initiating Direct-Acting Antiviral Agents in Patients with Hepatitis C Virus and Type 2 Diabetes Mellitus Using the United States Integrated Healthcare System.

Objective:Hepatitis C virus (HCV) has an increased risk of Type 2 diabetes mellitus (T2DM). Prior studies found that the eradication of HCV with direct-acting antiviral (DAA) agents led to improved glycemic control in patients with T2DM. We aimed to identify the association between HCV eradication and glycemic control in patients diagnosed with HCV and T2DM.Methods:A retrospective observational study was conducted to identify adult patients diagnosed with HCV from January 1, 2014, to August 31, 2017. Patients were included if they were initiated on one of the following DAA agents within the study period: Sofosbuvir/velpatasvir, sofosbuvir/ledispavir, elbasvir/grazopevir. Patients were also required to have the diagnosis of T2DM. The primary outcome of this study was the average change in glycosylated hemoglobin (HbA1c) pre- versus post-DAA agents.Findings:Our final cohort consisted of 996 patients diagnosed with HCV and T2DM: Patients who achieved sustained virologic response (SVR) (n = 937, 94%) and those who did not achieve SVR (n = 59, 6%). In the SVR group, there was a 0.3950% reduction in HbA1c (P < 0.0001) and in those who did not achieve SVR group, there was 0.3532% reduction in HbA1c (P = 0.0051). In the overall study population, SVR group had 0.04% more reduction in HbA1c but was not statistically significant (P = 0.7441).Conclusion:Both groups had statistically significant reductions in HbA1c when comparing the mean change in average HbA1c pre-versus post-DAA agent. Patients who achieved SVR had a greater absolute reduction in HbA1c by 0.04%; however, this was not statistically significant.

Factors associated with the glucose-lowering efficacy of sitagliptin in Japanese patients with type2 diabetes mellitus: Pooled analysis of Japanese clinical trials.

Aims/IntroductionTo explore the factors associated with the glucose‐lowering efficacy of sitagliptin treatment in Japanese patients with type 2 diabetes mellitus.Materials and MethodsThis was a post‐hoc analysis of pooled data from seven sitagliptin phase II and III clinical studies carried out in Japan. All studies were double‐blind, randomized, placebo‐controlled, parallel‐group and of 12‐week duration. The analysis population consisted of 1,075 type 2 diabetes mellitus patients. In two of the trials, sitagliptin 50 mg and/or 100 mg daily were used as monotherapy; in five others, sitagliptin 50 mg daily was used as add‐on treatment to ongoing pioglitazone, glimepiride, metformin, voglibose or glinides. Efficacy (reduction in hemoglobin A1c [HbA1c]) was evaluated in 12 sets of subgroups defined by demographic, glycemic, pancreatic β‐cell function and insulin resistance parameters. An analysis of covariance model was used to evaluate the interaction between each parameter and efficacy.ResultsSitagliptin consistently provided a clinically meaningful reduction in HbA1c relative to placebo across all subgroups. Within subgroups, a greater absolute HbA1c reduction was associated with higher baseline HbA1c, fasting plasma glucose and 2‐h post‐meal glucose. Lower β‐cell function, represented by homeostatic model assessment of β‐cell function and insulinogenic index, was also associated with greater HbA1c reduction. In contrast, age, sex, body mass index, duration of type 2 diabetes mellitus and insulin resistance‐related parameters did not interact with HbA1c changes.ConclusionsSitagliptin treatment was associated with clinically meaningful improvement in glycemic control in all subgroups of Japanese patients with type 2 diabetes mellitus that were evaluated. Higher baseline glycemic status and lower baseline β‐cell function were identified as factors associated with greater HbA1c reduction after sitagliptin treatment.

Improving HbA1c with Glucose Self-Monitoring in Diabetic Patients with EpxDiabetes, a Phone Call and Text Message-Based Telemedicine Platform: A Randomized Controlled Trial.

Background:We conducted a randomized controlled trial of EpxDiabetes, a novel digital health intervention as an adjunct therapy to reduce HbA1c and fasting blood glucose (FBG) among patients with type 2 diabetes mellitus (T2DM). In addition, we examined the effect of social determinants of health on our system.Methods:Sixty-five (n = 65) patients were randomized at a primary care clinic. Self-reported FBG data were collected by EpxDiabetes automated phone calls or text messages. Only intervention group responses were shared with providers, facilitating follow-up and bidirectional communication. ΔHbA1c and ΔFBG were analyzed after 6 months.Results:There was an absolute HbA1c reduction of 0.69% in the intervention group (95% confidence interval [CI], -1.41 to 0.02) and an absolute reduction of 0.03% in the control group (95% CI, -0.88 to 0.82). For those with baseline HbA1c >8%, HbA1c decreased significantly by 1.17% in the intervention group (95% CI, -1.90 to -0.44), and decreased by 0.02% in the control group (95% CI, -0.99 to 0.94). FBG decreased in the intervention group by 21.6 mg/dL (95% CI, -37.56 to -5.639), and increased 13.0 mg/dL in the control group (95% CI, -47.67 to 73.69). Engagement (proportion responding to ≥25% of texts or calls over 4 weeks) was 58% for the intervention group (95% CI, 0.373-0.627) and 48% for the control group (95% CI, 0.296-0.621). Smoking, number of comorbidities, and response rate were significant predictors of ΔHbA1c.Conclusions:EpxDiabetes helps to reduce HbA1c in patients with uncontrolled T2DM and fosters patient-provider communication; it has definite merit as an adjunct therapy in diabetes management. Future work will focus on improving the acceptability of the system and implementation on a larger scale trial.

Impact of clinical pharmacy specialists on glycemic control in veterans with type 2 diabetes.

The results of a study to determine the impact that Patient Aligned Care Team clinical pharmacy specialists (CPSs) have in improving glycemic control among veterans with type 2 diabetes are reported. Reductions in glycosylated hemoglobin (HbA1c) values in diabetic patients are associated with improved outcomes related to vascular complications. Current diabetes management strategies at the Cincinnati Veteran Affairs Medical Center (VAMC) involve a multidisciplinary approach that includes visits with a CPS by veterans referred by a primary care provider. A retrospective chart review-based study of veterans who received CPS care for diabetes management was conducted. The primary outcome was HbA1c reduction after up to 18 months of CPS care; subgroup analyses by type of clinic visit (face-to-face versus telephone), age group, Care Assessment Need (CAN) Score, and number of visits within an 18-month time frame were performed. There was a 2.2% absolute reduction in the mean HbA1c value among veterans receiving CPS care for up to 18 months. There was no statistically significant difference in absolute HbA1c reduction by type of clinic visit. The greatest absolute HbA1c reduction was observed in the following subgroups: 60- to 69-year-old veterans, veterans with a CAN score of ≥90, and veterans who had 5 or more CPS visits. CPSs at the Cincinnati VAMC significantly reduced the HbA1c of uncontrolled, complex diabetic veterans. The reduction in HbA1c was greatest in patients who had more than 5 encounters with a CPS over the 18-month data collection period.

Impact of the clinical pharmacy specialist in telehealth primary care.

A telehealth-based chronic disease management program including clinical pharmacy specialists (CPSs) and the program's impact on primary care outcomes in a population of veterans are described. A telehealth program including CPS services was developed to improve healthcare access and quality for veterans in rural areas of the Pacific Northwest. Outcomes of medication management services provided by a CPS team during both clinical video telehealth and telephone encounters with 554 patients from October 2014 to March 2017 were assessed. Patients were targeted for diabetes (DM), hyperlipidemia (HLD), and hypertension (HTN) control and tobacco cessation; the respective primary outcomes were the mean changes from baseline in glycosylated hemoglobin (HbA1c) and blood pressure values and rates of guideline-indicated statin therapy and tobacco cessation. Patients in the DM and HTN groups had a mean absolute HbA1c reduction of 1.61% (95% confidence interval [CI], 1.39-1.83%; p < 0.0001) and a mean systolic blood pressure reduction of 26.00 mm Hg (95% CI, 22.99-28.50 mm Hg; p < 0.001), respectively. In the HLD group, 93% of patients were discharged on a lipid-lowering medication. Tobacco cessation was achieved in 42% of targeted patients. CPSs providing primary care comprehensive medication management services solely via telehealth improved disease management and access to healthcare in a population of rural veterans. Statistically significant improvements in DM and HTN outcomes were demonstrated along with clinically significant improvements in the areas of lipid management and tobacco cessation.

Improvement of Glycosylated Hemoglobin in Patients with Type 2 Diabetes Mellitus under Insulin Treatment by Reimbursement for Self-Monitoring of Blood Glucose.

BackgroundIn Korea, the costs associated with self-monitoring of blood glucose (SMBG) for patients with type 2 diabetes mellitus (T2DM) under insulin treatment have been reimbursed since November 2015. We investigated whether this new reimbursement program for SMBG has improved the glycemic control in the beneficiaries of this policy.MethodsAmong all adult T2DM patients with ≥3 months of reimbursement (n=854), subjects without any changes in anti-hyperglycemic agents during the study period were selected. The improvement of glycosylated hemoglobin (HbA1c) was defined as an absolute reduction in HbA1c ≥0.6% or an HbA1c level at follow-up <7%.ResultsHbA1c levels significantly decreased from 8.5%±1.3% to 8.2%±1.2% during the follow-up (P<0.001) in all the study subjects (n=409). Among them, 35.5% (n=145) showed a significant improvement in HbA1c. Subjects covered under the Medical Aid system showed a higher prevalence of improvement in HbA1c than those with medical insurance (52.2% vs. 33.3%, respectively, P=0.012). In the improvement group, the baseline HbA1c (P<0.001), fasting C-peptide (P=0.016), and daily dose of insulin/body weight (P=0.024) showed significant negative correlations with the degree of HbA1c change. Multivariate analysis showed that subjects in the Medical Aid system were about 2.5-fold more likely to improve in HbA1c compared to those with medical insurance (odds ratio, 2.459; 95% confidence interval, 1.138 to 5.314; P=0.022).ConclusionThe reimbursement for SMBG resulted in a significant improvement in HbA1c in T2DM subjects using insulin, which was more prominent in subjects with poor glucose control at baseline or covered under the Medical Aid system.

One Drop | Mobile: An Evaluation of Hemoglobin A1c Improvement Linked to App Engagement.

BackgroundThree recent reviews evaluated 19 studies testing the hemoglobin A1c (HbA1c) benefit of 16 diabetes apps, including 5 publicly available apps. Most studies relied on small samples and did not link app engagement with outcomes.ObjectiveThis study assessed both HbA1c change in a large sample of people using the One Drop | Mobile app and associations between app engagement and changes in HbA1c.MethodsThe One Drop | Mobile app for iOS and Android is designed to manually and passively (via Apple HealthKit, Google Fit, and the One Drop | Chrome blood glucose meter) store, track, and share data. Users can schedule medication reminders, view statistics, set goals, track health outcomes, and get data-driven insights. In June 2017, we queried data on people with diabetes using the app who had entered at least 2 HbA1c values in the app >60 and ≤365 days apart. Multiple imputation corrected for missing data. Unadjusted and adjusted mixed effects repeated measures models tested mean HbA1c change by time, diabetes type, and their interaction. Multiple regression models assessed relationships between using the app to track food, activity, blood glucose, and medications and HbA1c change.ResultsThe sample (N=1288) included people with type 1 diabetes (T1D) (n=367) or type 2 diabetes (T2D) (n=921) who were 35% female, diagnosed with diabetes for a mean 9.4 (SD 9.9) years, and tracked an average 1646.1 (SD 3621.9) self-care activities in One Drop | Mobile between their first (mean 8.14% [SD 2.06%]) and second HbA1c entry (mean 6.98% [SD 1.1%]). HbA1c values were significantly associated with user-entered average blood glucose 90 days before the second HbA1c entry (rho=.73 to .75, P<.001). HbA1c decreased by an absolute 1.07% (unadjusted and adjusted F=292.03, P<.001) from first to second HbA1c entry. There was a significant interaction between diabetes type and HbA1c. Both groups significantly improved, but users with T2D had a greater HbA1c decrease over time than users with T1D (F=10.54, P<.001). For users with T2D (n=921), HbA1c decreased by an absolute 1.27% (F=364.50, P<.001) from first to second HbA1c entry. Finally, using One Drop | Mobile to record food was associated with greater HbA1c reductions even after adjusting for covariates and after also adjusting for insulin use for users with T2D (all P<.05).ConclusionsPeople with T1D and T2D reported a 1.07% to 1.27% absolute reduction in HbA1c during a median 4 months of using the One Drop | Mobile app. Using the app to track self-care was associated with improved HbA1c. More research is needed on the health benefits of publicly available diabetes apps, particularly studies associating app engagement with short- and long-term effects.

Improving Glycemic Control With a Standardized Text-Message and Phone-Based Intervention: A Community Implementation

BackgroundType II diabetes mellitus (T2DM) presents a major disease burden in the United States. Outpatient glycemic control among patients with T2DM remains difficult. Telemedicine shows great potential as an adjunct therapy to aid in glycemic control in real-world settings.ObjectiveWe aimed to explore the effectiveness of EpxDiabetes, a novel digital health intervention, in improving hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) among patients with uncontrolled diabetes.MethodsWe recruited 396 patients from a community clinic in St. Louis, Missouri, from a database of patients diagnosed with T2DM and with a most recent HbA1c >7% as part of a quality improvement project. An automated call or text-messaging system was used to monitor patient-reported FBG. If determined to be elevated, care managers were notified by email, text, or electronic medical record alert. Participants self-reported their FBG data by replying to EpxDiabetes automated phone calls or text messages. Data were subsequently analyzed, triaged, and shared with providers to enable appropriate follow-up and care plan adjustments. Absolute HbA1c reduction, patient engagement, and absolute patient-reported FBG reduction were examined at approximately 6 months post implementation.ResultsEpxDiabetes had an average 95.6% patient response rate to messages at least once per month and an average 71.1% response rate to messages at least once per week. Subsequent HbA1c drop with EpxDiabetes use over 4 months was -1.15% (95% CI -1.58 to -0.71) for patients with HbA1c >8% at baseline compared to the change in HbA1c over 4 months prior to the implementation of EpxDiabetes of only -0.005 points (95% CI -0.28 to 0.27), P=.0018.ConclusionsEpxDiabetes may help reduce HbA1c in patients with high HbA1c baselines (>8%). The intervention demonstrates high patient engagement sustainable for at least 6 months.

Effectiveness of vildagliptin as add-on to metformin monotherapy among uncontrolled type 2 diabetes mellitus patients in a real-world setting.

Vildagliptin is a dipeptidyl peptidase-4 inhibitor commonly used as a dual oral agent with metformin, thiazolidinediones, or sulfonylurea for the treatment of type 2 diabetes mellitus (T2DM). The efficacy of dual therapy with vildagliptin and metformin has been established in randomized controlled trials, but there is little evidence from observational studies. The aims of the present study were to evaluate the effectiveness of vildagliptin as an add-on therapy to metformin in reducing HbA1c and its affects on body weight and blood lipids in a real-life setting. Included in the present retrospective cohort were T2DM patients (n = 345) who were uncontrolled on metformin monotherapy and intensified treatment with vildagliptin. The efficacy of at least 90 days of dual therapy with vildagliptin and metformin in reducing HbA1c levels, as well as changes in blood lipids and body weight, were evaluated. After 180 days (range 90-365 days) from the index date with a mean daily dose of 92 mg vildagliptin, HbA1c was significantly (P < 0.001) reduced by an average of 0.9% (95% confidence interval -1.0%, -0.7%). The absolute reduction in HbA1c was positively associated with baseline HbA1c levels. In addition to HbA1c, a modest but significant (P < 0.05) decrement was also calculated in the patients' body weight and blood lipids. The present analysis of real-world data corroborates the results of previous randomized controlled trials indicating that add-on therapy with vildagliptin in uncontrolled patients on metformin monotherapy is associated with a significant improvement in the control of HbA1c.

Early Glycemic Control and Magnitude of HbA1c Reduction Predict Cardiovascular Events and Mortality: Population-Based Cohort Study of 24,752 Metformin Initiators.

We investigated the association of early achieved HbA1c level and magnitude of HbA1c reduction with subsequent risk of cardiovascular events or death in patients with type 2 diabetes who initiate metformin. This was a population-based cohort study including all metformin initiators with HbA1c tests in Northern Denmark, 2000-2012. Six months after metformin initiation, we classified patients by HbA1c achieved (<6.5% or higher) and by magnitude of HbA1c change from the pretreatment baseline. We used Cox regression to examine subsequent rates of acute myocardial infarction, stroke, or death, controlling for baseline HbA1c and other confounding factors. We included 24,752 metformin initiators (median age 62.5 years, 55% males) with a median follow-up of 2.6 years. The risk of a combined outcome event gradually increased with rising levels of HbA1c achieved compared with a target HbA1c of <6.5%: adjusted hazard ratio (HR) 1.18 (95% CI 1.07-1.30) for 6.5-6.99%, HR 1.23 (1.09-1.40) for 7.0-7.49%, HR 1.34 (1.14-1.57) for 7.5-7.99%, and HR 1.59 (1.37-1.84) for ≥8%. Results were consistent for individual outcome events and robust by age-group and other patient characteristics. A large absolute HbA1c reduction from baseline also predicted outcome: adjusted HR 0.80 (0.65-0.97) for Δ = -4, HR 0.98 (0.80-1.20) for Δ = -3, HR 0.92 (0.78-1.08) for Δ = -2, and HR 0.99 (0.89-1.10) for Δ = -1 compared with no HbA1c change (Δ = 0). A large initial HbA1c reduction and achievement of low HbA1c levels within 6 months after metformin initiation are associated with a lower risk of cardiovascular events and death in patients with type 2 diabetes.