Potential Roles of Glucagon-Like Peptide 1 Receptor Agonists (GLP-1 RAs) in Nondiabetic Populations
Table 2
Summary of GLP-1 RA preventive effects in DM and non-DM patients.
DM
Non-DM
CKD prevention
GLP-1 RA reduce albuminuria and modify risk factors and reduction of a broad kidney composite outcome by 17%. Recommended in CKD.
No human trials yet. CVOT in T2DM suggest renoprotective effects with corrected for glycaemic control.
CVD prevention
GLP-1 RA reduce MACE in CVOT by 14% and a slightly lower risk of hospitalization for HF by 9%, reduction in all-cause mortality by 12%.
No direct trials yet. GLP-1 RAs for 7 days make a mild improvement of left ventricular function in patients with ST-segment elevation myocardial infarction (STEMI) as well as non-STEMI.
Dyslipidaemia, hypertension, and nonalcoholic fatty liver disease (NAFLD) prevention
No direct trials for GLP-1 RA on hypertension, NAFLD, and dyslipidaemia. CVOTs showed reduction of BP and dyslipidaemia, consistent with reduced all-cause mortality
Liraglutide vs. placebo in obese patients, BP, and fasting lipids lower with liraglutide. Liraglutide vs. placebo in obese patients, more frequent resolution of NAFLD, and less progression to fibrosis. Meta-analysis shows GLP-1 RA reduce ALT and improve NAFLD.
Prevention of PCOS, metabolic, and cardiovascular complications
GLP-1 RA improve insulin sensitivity and weight control, and therefore hyperandrogenism and metabolic complications in PCOS. Exenatide vs. metformin, exenatide induce remission of 56% of prediabetes in PCOS.
Open-label trial liraglutide, reduce weight. RCT liraglutide vs. metformin, liraglutide reduce BMI. RCT exenatide vs. metformin, exenatide lower BMI. Open-label trial exenatide, BMI -1 to -3.1. Exenatide vs. metformin, exenatide increase fertility, frequency and regularity of periods, and ovulatory rate.
Obesity & overweight prevention
GLP-1 RAs proven to induce weight loss and improve glycaemic control. Liraglutide body weight loss of 5.8% Semaglutide body weight loss of 6.9-9.6%
Pharmacotherapy for or overweight with complications. RCT diet+exercise+/-liraglutide, found BMI -3+/-2.6 with liraglutide. RCT liraglutide vs. semaglutide vs. placebo, found 7.8% LOW with liraglutide, and 11-14% LOW with semaglutide.
Prevention of perioperative and postoperative complications of bariatric surgery
GLP-1 RA known to improve glycaemic control and treat the persistent/recurrent T2DM postbariatric surgery. No human trials yet investigating role of GLP-1 RA in success of bariatric surgery.
No human trials yet. GLP-1 rises after bariatric surgery and prevent the onset of T2DM postbariatric surgery.
