Efficacy and safety of combination of semaglutide and basal insulin in patients with of type 2 diabetes mellitus: A systematic review and meta-analysis

Clin Nutr ESPEN. 2025 Apr:66:564-572. doi: 10.1016/j.clnesp.2025.01.056. Epub 2025 Jan 30.

Abstract

Background & aims: Semaglutide has demonstrated efficacy in both glycemic control and weight loss. This systematic review and meta-analysis aimed to assess the efficacy and safety of the combined use of semaglutide and basal insulin in individuals diagnosed with type 2 diabetes mellitus (T2DM).

Methods: PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (VIP) were searched to identify relevant publications. The primary outcome measure was the change in HbA1c levels. Secondary outcome measures encompassed change in body weight, fluctuations in FPG levels, occurrence of adverse events, serious adverse events, hypoglycemic episodes, and gastrointestinal reactions including nausea, vomiting, and diarrhea. Mean differences (MDs) and relative risk (RR) with confidence intervals (CI) of 95 % were used to analyze the deference.

Results: 7 RCTs with 2354 patients were incorporated into the study. Compared to placebo or other active treatment, the addition of semaglutide to basal insulin demonstrated significant reductions in hemoglobin A1c (HbA1c) [mean differences (MD): -1.17 %, P < 0.00001], body weight [MD -5.99 kg, P < 0.00001], and fasting blood glucose (FPG) [MD -1.08 %, P < 0.00001]. No evidence indicated a higher risk of adverse events [RR 1.46, P = 0.13]. However, it did result in increased rates of gastrointestinal adverse events, including nausea, vomiting and diarrhea.

Conclusions: The combination treatment of semaglutide and basal insulin demonstrates significant improvements in glycemic control and reduction in body weight, without an increased risk of hypoglycemia. Our findings provided support for the utilization of a combination therapy involving semaglutide and basal insulin in T2DM.

Keywords: Glucagon-like peptide-1 receptor agonists; HbA1c; Insulin; Semaglutide; Type 2 diabetes mellitus.

Publication types

  • Systematic Review
  • Meta-Analysis

MeSH terms

  • Blood Glucose / drug effects
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / drug therapy
  • Drug Therapy, Combination
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides* / administration & dosage
  • Glucagon-Like Peptides* / adverse effects
  • Glucagon-Like Peptides* / therapeutic use
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents* / administration & dosage
  • Hypoglycemic Agents* / adverse effects
  • Hypoglycemic Agents* / therapeutic use
  • Insulin Glargine* / therapeutic use
  • Insulin* / administration & dosage
  • Insulin* / adverse effects
  • Insulin* / therapeutic use
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Substances

  • Glucagon-Like Peptides
  • semaglutide
  • Hypoglycemic Agents
  • Glycated Hemoglobin
  • Blood Glucose
  • Insulin
  • Insulin Glargine
  • hemoglobin A1c protein, human
  • Glucagon-Like Peptide 1