Tirzepatide is a combined glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist. This review will summarize the pharmacological aspects of tirzepatide with a focus on the clinical efficacy and safety reported in the trial programs underlying the regulatory approval for the treatment of type 2 diabetes (T2D) and obesity in the U.S. and Europe. In a range of trials, tirzepatide has been compared to placebo, insulin and GLP-1 mono-receptor agonists. The trials have included participants with T2D (SURPASS) and obesity (SURMOUNT-1) and have examined tirzepatide in doses ranging from 5 to 15 mg administered once weekly. In the SURPASS trials, tirzepatide led to dose-dependent clinically relevant reductions in HbA1c of up to 20-28 mmol/mol. A head-to-head trial comparing tirzepatide (5-15 mg once weekly) to the GLP-1 mono-receptor agonist semaglutide (1 mg once weekly) demonstrated all doses of tirzepatide to be superior with respect to HbA1c reduction. In terms of body weight, tirzepatide 5-15 mg caused reductions from baseline of up to 13% in patients with T2D in the SURPASS trials and up to 21% in nondiabetic participants in the SURMOUNT-1 trial. The most frequent adverse events were gastrointestinal symptoms with nausea as the most frequently observed adverse event in up to 33% of tirzepatide (15 mg)-treated patients. These gastrointestinal symptoms were dose-dependent and often self-limiting with a lower occurrence compared to GLP-1 mono-receptor agonists at conditions with similar efficacy (i.e., with similar HbA1c and body weight reduction). Adverse events resulted in trial drop-out rates from 3-11% of all patients treated with tirzepatide. The potential superior efficacy of tirzepatide compared to GLP- 1 mono-receptor agonists is hypothesized to be a result of the unique dual GLP-1 and GIP receptor agonism. At present, there is no data to support long-term efficacy and safety of tirzepatide. Ongoing trials reporting results the coming years on cardiovascular effects as well as the clinical use in specific populations will unravel the full clinical potential for tirzepatide.