MedicineOct 31, 2023

Comparing long-acting and short-acting GLP-1 drugs for weight loss and metabolism in type 2 diabetes

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Mar 29, 2026

Abstract

Twelve randomized controlled trials involving 2751 patients were analyzed to compare the effects of long-acting and short-acting GLP-1 receptor agonists.

Long-acting GLP-1 receptor agonists led to a greater reduction in body weight compared to short-acting ones.
A significant improvement in glycosylated hemoglobin (HbA1c) levels was observed with long-acting GLP-1 receptor agonists.
Fasting plasma glucose levels decreased more with long-acting GLP-1 receptor agonists than with short-acting counterparts.
Long-acting GLP-1 receptor agonists were associated with a greater reduction in total cholesterol and low-density lipoprotein (LDL) levels.
No significant treatment differences were found for triglycerides and high-density lipoprotein (HDL) levels.

Simplified

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) showed great value in treating nonalcoholic fatty liver disease (NAFLD). We aimed to compare the effectiveness of long-acting and short-acting GLP-1RAs on improving body weight and related metabolic parameters in patients with type 2 diabetes (T2DM) as a reference for the treatment of NAFLD with T2DM.

METHODS: We searched eligible randomized controlled trials (RCTs) in PubMed, Embase, Cochrane and web of science database until August 2023. The risk of bias of included RCTs were assessed by the Risk Assessment of Cochrane Review items. We mainly drew forest plots to compare the effects of long and short acting GLP-1 RAs using RevMan 5.4.

RESULTS: Twelve RCTs involving 2751 patients were included in our meta-analysis. Compared with short-acting GLP-1 RAs, the long-acting group was better in body weight (P < .00001, MD = -0.65, 95% confidence interval [CI] [-0.90, -0.40], I2 = 20%), and the same results in glycosylated hemoglobin (HbA1c) (P < .00001, MD = -0.43, 95% CI [-0.54, -0.33], I2 = 55%) and fasting plasma glucose (FPG) (P < .00001, MD = -0.77, 95% CI [-1.01, -0.52], I2 =70%). For the lipid parameters, long-acting drugs lowered cholesterol (TC) (P = .02, SMD = -0.19, 95% CI [-0.35, -0.03], I2 =57%) and low-density lipoprotein (LDL) (P = .02, SMD = -0.17, 95% CI [-0.33, -0.02], I2 =51%) more significantly compared with short-acting drugs. But treatment differences were not significant in triglycerides (TG) (P = .40, SMD = -0.05, 95% CI [-0.15, -0.06], I2 = 0%), and high-density lipoprotein (HDL) (P = .85, SMD = -0.01, 95% CI [-0.11, -0.09], I2 = 0%).

CONCLUSION: Long-acting GLP-1RAs may be more promise than short-acting GLP-1RAs in improving weight and related metabolic parameters.

Key numbers

-0.65

Weight Loss Reduction

Mean difference in body weight from baseline.

-0.43

HbA1c Reduction

Mean difference in HbA1c levels.

-0.77

Fasting Plasma Glucose Reduction

Mean difference in fasting plasma glucose levels.

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Comparing long-acting and short-acting GLP-1 drugs for weight loss and metabolism in type 2 diabetes

Abstract

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