Efficacy and safety of incretin-based drugs in patients with type 1 diabetes mellitus: A systematic review and meta-analysis

Diabetes Res Clin Pract. 2017 Jul;129:213-223. doi: 10.1016/j.diabres.2017.05.007. Epub 2017 May 12.


Aims: In patients with type 2 diabetes, incretin-based therapies can improve glucose control without increased weight gain or hypoglycemia. Incretin-based drugs added to insulin therapy in type 1 diabetes (T1DM) have also been tried in many studies. However, the results were controversial. We thus performed a meta-analysis to assess the efficacy and safety of incretin-based therapies in patients with T1DM.

Methods: We systematically searched Medline, EMBASE, and Cochrane Central Register of Controlled Trials for relevant studies published before August 25, 2016. Data was extracted by two independent reviewers. The main outcomes included glycosylated hemoglobin (HbA1c), insulin dose, weight, hypoglycemia, ketosis and ketoacidosis. All pooled data were assessed using random-effects model.

Results: Twelve randomized controlled trials with a total of 2903 individuals were finally included into the meta-analysis. Incretin-based drugs could significantly reduce HbA1c (MD -0.20, 95% CI -0.30 to -0.10), weight (MD -2.83, 95% CI -4.00 to -1.65) and insulin dose (MD -4.55, 95% CI -6.15 to -2.94). Furthermore, incretin-based drugs did not increase relative risk of severe hypoglycemia (RR 0.79, 95% CI 0.58 to 1.06), ketosis (RR 1.37, 95% CI 0.95 to 1.97) and ketoacidosis (RR 2.62, 95% CI 0.31 to 21.99).

Conclusions: Incretin-based treatment in patients with T1DM may improve glycemic control and reduce insulin dose and weight without increasing the risk of serious adverse event, such as severe hypoglycemia, ketosis or ketoacidosis. The current evidence for the aforementioned adverse effects, however, is weak. A rigorous monitoring of these adverse events should be implemented in well-designed observational studies.

Keywords: DPP-4; GLP-1; Incretin; Type 1 diabetes.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / pathology
  • Female
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Incretins / pharmacology
  • Incretins / therapeutic use*
  • Male
  • Middle Aged
  • Risk
  • Young Adult


  • Hypoglycemic Agents
  • Incretins