Certain populations may need modifications to the dose schedule based on their unique physiological characteristics
Most studies have found a decrease in GLP-1 secretion in obese individuals [92], and some studies have found no difference in GLP-1 levels between obese and normal-weight controls [93]
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Type 2 Diabetes Research Glycemic Control Studies Phase 2 investigations in adults with type 2 diabetes demonstrated dual benefits on both glucose control and body weight[13]: HbA1c reductions of 1.39% to 2.02% with GLP3 at 4 mg to 12 mg at 24 weeks Body weight reductions of 7.92% to 16.94% at 36 weeks depending on dose 72% of participants with prediabetes at baseline reverted to normoglycemia with GLP3 treatment Improvements in fasting glucose, insulin levels, and measures of insulin sensitivity Effects exceeded those observed with dulaglutide (a GLP-1 receptor agonist) comparator Beta Cell Function and Insulin Sensitivity Mechanistic studies in participants with type 2 diabetes revealed: Enhanced markers of pancreatic beta cell function Improved insulin sensitivity indices Sustained glycemic control throughout 36-week treatment period Glucose-lowering effects observed even in participants with relatively preserved beta cell function Cardiometabolic Effects Research Lipid Profile Improvements Clinical trials documented significant improvements in cardiovascular risk markers[14]: Low-density lipoprotein cholesterol reductions of approximately 20% Triglyceride reductions of up to 50% with higher doses VLDL cholesterol decreases paralleling triglyceride improvements Minimal changes in HDL cholesterol levels Potential mechanisms include glucagon receptor-mediated effects on PCSK9 degradation Blood Pressure and Cardiac Parameters Cardiovascular monitoring in phase 2 trials revealed: Systolic blood pressure reductions of 5 to 10 mmHg depending on dose Diastolic blood pressure improvements of 3 to 5 mmHg Dose-dependent increases in heart rate (peak at 24 weeks, declining thereafter) Heart rate changes similar to those observed with other GLP-1 or GLP-1/GIP receptor agonists Body Composition Research A dedicated substudy examined the quality of weight loss using dual-energy X-ray absorptiometry (DEXA) scans[15]: Total body fat mass reductions significantly greater than placebo and dulaglutide comparator Proportion of lean mass loss to total weight loss similar to other obesity treatments (approximately 25-30%) Preferential reduction in visceral adipose tissue compared to subcutaneous fat Preservation of lean mass relative to overall weight loss comparable to surgical weight loss interventions [CALLOUT BOX Highlighted] Critical Limitation: All published efficacy data derive from clinical trials lasting 48 weeks or less

Eduardo Grunvald, Medical Director of the University of California San Diego's Center for Advanced Weight Management, has noted, the more total weight you lose, the more muscle mass you tend to lose, though he is clear that the benefits of treating obesity outweigh that risk
Diabetes 47:10461052 Migoya EM, Bergeron R, Miller JL et al (2010) Dipeptidyl peptidase-4 inhibitors in combination with metformin result in an additive increase in active GLP-1 concentrations