Sheep Anti-Human Glucagon (C-Terminal) Polyclonal Antibody

Background: The global incidence of type 2 diabetes (T2D) continues to increase annually, and persons with T2D typically require regular changes in pharmacologic invention for achieving glycemic targets. Healthcare providers must consider multiple factors when selecting a 2nd line. This retrospective cohort study evaluates impact of two common anti-diabetes medication classes (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) on the well-known composite 3-point major cardiovascular events outcome (3P-MACE, comprised of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). No significant impact was found. Persons with T2D face increased risks of many adverse cardiovascular outcomes. This study duplicated common inclusion and exclusion criteria to create an observational cohort from a large healthcare system's electronic health records for testing DPP-4i and GLP-1RA against each other to evaluate impact on likelihood to develop 3P-MACE. Methods: The statistical model and analyses were based on a cohort of 5,518 adult patients with T2D who were prescribed metformin and either DPP-4i or GLP-1RA to control glycemia during clinic visits between January 2005 and September 2019. A Cox proportional hazards model was developed from the cohort to predict the 3P-MACE endpoint. Results: The model did not show a meaningful difference in likelihood of developing the 3P-MACE outcome between patients treated with DPP-4i compared to patients treated with GLP-1RA. Conclusions: Prior history of cardiovascular disease (CVD) did not impact this small difference between the two classes of drug.

Aim: To examine how circulating glucagon-like peptide-1 (GLP-1) concentrations during liraglutide treatment relate to its therapeutic actions on glucose and weight, and to study the effects of liraglutide on other proglucagon-derived peptides (PGDPs), including endogenous GLP-1, glucagon-like peptide-2, glucagon, oxyntomodulin, glicentin and major proglucagon fragment, which also regulate metabolic and weight control. Materials and Methods: Adults who were overweight/obese (body mass index 27-40 kg/m(2)) with prediabetes were randomized to liraglutide (1.8 mg/day) versus placebo for 14 weeks. We used specific assays to measure exogenous (liraglutide, GLP-1 agonist [GLP-1A]) and endogenous (GLP-1E) GLP-1, alongside five other PGDP concentrations during a mixed meal tolerance test (MMTT) completed at baseline and at week 14 (liraglutide, n = 16; placebo, n = 19). Glucose during MMTT, steady-state plasma glucose (SSPG) concentration for insulin resistance and insulin secretion rate (ISR) were previously measured. MMTT area-under-the-curve (AUC) was calculated for ISR, glucose and levels of PGDPs. Results: Participants on liraglutide versus placebo had significantly (P <= .004) decreased weight (mean -3.6%, 95% CI [-5.2% to -2.1%]), SSPG (-32% [-43% to -22%]) and glucose AUC (-7.0% [-11.5% to -2.5%]) and increased ISR AUC (30% [16% to 44%]). GLP-1A AUC at study end was significantly (P <= .04) linearly associated with % decrease in weight (r = -0.54) and SSPG (r = -0.59) and increase in ISR AUC (r = 0.51) in the liraglutide group. Treatment with liraglutide significantly (P <= .005) increased exogenous GLP-1A AUC (median 310 vs. 262 pg/mL x 8 hours at baseline but decreased endogenous GLP-1E AUC [13.1 vs. 24.2 pmol/L x 8 hours at baseline]), as well as the five other PGDPs. Decreases in the PGDPs processed in the intestines are independent of weight loss, indicating a probable direct effect of GLP-1 receptor agonists to decrease their endogenous production in contrast to weight loss-dependent changes in glucagon and major proglucagon fragment that are processed in pancreatic alpha cells. Conclusions: Circulating GLP-1A concentrations, reflecting liraglutide levels, predict improvement in weight, insulin action and secretion in a linear manner. Importantly, liraglutide also downregulates other PGDPs, normalization of the levels of which may provide additional metabolic and weight loss benefits in the future.