Summary

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• This summary is based on the review of 27 systematic review(s)/meta-analysis(es). ^[1-27]
• Reduction in Glycated Hemoglobin (HbA1c): Tirzepatide demonstrated superior efficacy in lowering HbA1c across multiple doses, with the 15 mg dose showing the most significant reduction (mean difference (MD) -1.27, 95% confidence interval (CI) -1.49; -1.0). Reductions compared to placebo ranged from -1.62% to -2.06%, and greater reductions were observed compared to glucagon-like peptide-1 receptor agonists (GLP-1RAs) and basal insulin.
• Reduction in Fasting Plasma Glucose (FPG): Tirzepatide significantly reduced FPG levels, with the 15 mg dose achieving the highest reduction (MD -0.70, 95% CI -1.05; -0.34), with reductions compared to placebo reaching up to -54.72 mg/dL.
• Body Weight Reduction: Tirzepatide showed significant weight loss, with the 15 mg dose resulting in the most pronounced reduction (MD -12.13, 95% CI -13.98; -10.27). Weight reductions compared to placebo ranged from -8.47 kg to -11.33 kg, surpassing those achieved by GLP-1RAs and basal insulin.
• Lipid Profile and Cardiovascular Outcomes: Tirzepatide reduced triglycerides and increased high-density lipoprotein (HDL) cholesterol, with no observed increase in the risk of major adverse cardiovascular events (MACE).
• Adverse Events (AEs): Tirzepatide was associated with a higher incidence of gastrointestinal AEs, including nausea, vomiting, diarrhea, dyspepsia, decreased appetite, and constipation, with higher doses leading to more AEs. Similar gastrointestinal AEs were observed with glucagon-like peptide 1 (GLP-1) receptor agonists, while basal insulin showed a lower incidence of gastrointestinal AEs.
• Hypoglycemia: Tirzepatide did not significantly increase the risk of severe hypoglycemia compared to placebo, and had lower incidences of hypoglycemia compared to basal insulin.
• Serious Adverse Events: There was no significant increase in serious adverse events or mortality with tirzepatide compared to placebo, GLP-1 receptor agonists, or basal insulin. However, tirzepatide was associated with a higher risk of gallbladder or biliary diseases compared to placebo and basal insulin, though it did not increase the risk of pancreatitis.
• Non-Asians experienced greater reductions in fasting blood glucose (FBG) and HbA1c levels compared to Asians, while Asians showed more significant weight loss. Asians also had a higher incidence of gastrointestinal adverse events (AEs), whereas non-Asians had a higher incidence of metabolic and nutritional disorders. Additionally, tirzepatide demonstrated the most significant reductions in HbA1c and body weight in Japanese patients. In patients with high cardiovascular risk, tirzepatide did not increase the risk of MACE, cardiovascular death, or all-cause mortality.