Impact of insulin and metformin versus metformin alone on beta-cell function in youth with impaired glucose tolerance or recently diagnosed type 2 diabetes

Author(s):  
Consortium Bai RISE
2003 ◽  
Vol 3 (1_suppl) ◽  
pp. S24-S40 ◽  
Author(s):  
Ralph A Defronzo

Lifestyle intervention prevents or delays the conversion from impaired glucose tolerance (IGT) to type 2 diabetes. However, many subjects fail to achieve and/or maintain long-term weight loss and to follow a regular exercise regimen may require pharmacologic therapy. Insulin resistance in liver, muscle and fat, along with impaired beta-cell function, plays a central role in the pathogenesis of type 2 diabetes. Insulin sensitising drugs, including metformin and the thiazolidinediones, have significantly reduced the conversion rate of IGT to type 2 diabetes in subjects in several large, well designed clinical trials. Insulin-sensitising drugs are likely to play an important role in future strategies for diabetes prevention.


2015 ◽  
Vol 100 (10) ◽  
pp. 3744-3751 ◽  
Author(s):  
Teresa Vanessa Fiorentino ◽  
Maria Adelaide Marini ◽  
Francesco Andreozzi ◽  
Franco Arturi ◽  
Elena Succurro ◽  
...  

Context: Subjects with normal glucose tolerance (NGT) but 1-h postload glucose ≥ 155 mg/dL (NGT-1h-high) exhibit an intermediate cardiometabolic risk profile between individuals with NGT and impaired glucose tolerance (IGT). Objective: This study aimed to evaluate whether NGT-1h-high subjects have different cardiometabolic characteristics and an increased risk of type 2 diabetes compared with individuals with isolated impaired fasting glucose (IFG). Setting, Design, and Patients: A cross-sectional analysis was performed on 595 nondiabetic subjects who underwent an oral glucose tolerance test and an euglycemic hyperinsulinemic clamp in an ambulatory care setting. In addition, a longitudinal analysis was performed on 392 individuals, who were reexamined after a followup of 5.2 ± 0.9 y. Main Outcome Measures: Insulin sensitivity, beta-cell function, and risk of developing diabetes were measured. Results: Subjects with NGT-1h-high have a significant reduction of peripheral insulin sensitivity and beta-cell function, assessed by the disposition index, compared with either 1-h postload glucose < 155 mg/dL (NGT-1h-low) or IFG individuals, but not compared with IGT. Among the 392 subjects studied in the longitudinal analysis the incidence rate of type 2 diabetes over the follow-up period was 2.9, 16.7, 12.5, and 31.4% for subjects with NGT-1h-low, NGT-1h-high, IFG, and IGT, respectively. In a Cox proportional hazard regression analysis the risk of developing diabetes for NGT-1h-high subjects was 4.02 (95% confidence interval [CI] 1.06–15.26); an even higher risk (6.67; 95% CI, 2.09–21.24) was observed in subjects with IGT, but not in the isolated IFG group (1.91; 95% CI, 0.44–8.29). Conclusions: NGT-1h-high subjects exhibit a higher risk of developing diabetes than those with IFG or NGT-1h-low, likely due to decreased insulin sensitivity and beta-cell function.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1561-P
Author(s):  
SUZANNE CRAFT ◽  
AMY CLAXTON ◽  
MARK TRIPPUTI ◽  
SHARON EDELSTEIN ◽  
SILVA A. ARSLANIAN ◽  
...  

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 78-OR
Author(s):  
FARHAT FATIMA ◽  
JØRAN HJELMESÆTH ◽  
KARE I. BIRKELAND ◽  
HANNE L. GULSETH ◽  
JENS K. HERTEL ◽  
...  

2021 ◽  
Vol 9 (1) ◽  
pp. e002208
Author(s):  
Marcus Hompesch ◽  
Jahoon Kang ◽  
OakPil Han ◽  
Michael E Trautmann ◽  
Christopher H Sorli ◽  
...  

IntroductionTo evaluate the effects of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), on gastric emptying, glucose metabolism, and islet beta-cell function versus liraglutide and placebo in people with type 2 diabetes.Research design and methodsThis phase Ib study (ClinicalTrials.gov identifier: NCT02059564) randomized participants (n=47) to three cohorts. Within the first two cohorts, participants were randomized to placebo, efpeglenatide 6 mg weekly (QW; first cohort), or efpeglenatide 16 mg monthly (QM; second cohort). The third cohort received liraglutide 1.8 mg daily (QD). Gastric emptying was assessed through the pharmacokinetic (PK) profile of acetaminophen at baseline and steady state. Glucose metabolism and beta-cell function were assessed based on mixed-meal tolerance testing and a graded glucose infusion procedure.ResultsTreatment duration was approximately 3 months for efpeglenatide 16 mg QM and 1 month for efpeglenatide 6 mg QW and liraglutide. At peak drug concentrations, efpeglenatide 6 mg QW was non-inferior to liraglutide 1.8 mg QD in delaying gastric emptying, as assessed by acetaminophen PK (lower bound of 90% CI for the efpeglenatide:liraglutide ratio >0.8 for area under the curve (AUC)0–120, AUC0–180, AUC0–360 and maximum concentration (Cmax)). Efpeglenatide 16 mg QM did not decrease the rate of gastric emptying to as great an extent as liraglutide (ie, non-inferiority was not shown). Compared with liraglutide, both efpeglenatide dosing regimens demonstrated comparable or more favorable glucometabolic effects and improved beta-cell function. All gastrointestinal adverse events reported with efpeglenatide were mild or moderate in severity and transient over treatment and follow-up.ConclusionsThe glucometabolic effects of efpeglenatide 6 mg QW and 16 mg QM were comparable to liraglutide. Additional studies are necessary to further examine these benefits of efpeglenatide.Trial registration numberNCT02059564.


2000 ◽  
Vol 50 ◽  
pp. 108 ◽  
Author(s):  
Meng H. Tan ◽  
Sethu Reddy ◽  
Jean Abram ◽  
Pantelis Andreou ◽  
Danita Volder

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