CLINICAL QUESTION

In a patient with obesity and prediabetes, does giving a medication that lowers blood sugar help them lose weight and reduce the likelihood that they will develop type 2 diabetes?

BOTTOM LINE

Tirzepatide is an effective drug for weight loss, and the authors also found that it can prevent a diagnosis of type 2 diabetes in patients with obesity and prediabetes (number needed to treat [NNT] = 8 over 3.4 years). But it seems this is just treating prediabetes by giving patients with elevated blood sugar levels a drug that lowers blood sugar. It is not clear that doing this reduces the long-term incidence of cardiorenal complications or mortality. Tirzepatide is a good drug for the treatment of obesity and type 2 diabetes, but it should not be recommended to prevent type 2 diabetes as the sole rationale. (Level of Evidence = 1b)

SYNOPSIS

Tirzepatide is a dual glucose-dependent insulinotropic poly-peptide and glucagon-like peptide-1 receptor agonist that is approved for the treatment of obesity and type 2 diabetes. In the study, 1,032 patients with obesity and prediabetes (defined as a fasting blood glucose level between 100 mg/dL [5.55 mmol/L] and 125 mg/dL [6.94 mmol/L] or an A1C level between 5.7% and 6.4%) were randomized to receive one of three doses of tirzepatide (5 mg, 10 mg, or 15 mg subcutaneously once per week) or placebo injection. At baseline, the participants' mean age was 48 years, 64% were female, and 27% were non-White. The mean A1C level was 5.76% and the mean fasting glucose level was 101 mg/dL (5.61 mmol/L), so these patients were barely into prediabetes range. Groups were balanced and analysis was by intention to treat. Adherence was only fair, with 64% of patients being adherent to the regimen and 66% completing the full 193 weeks (3.7 years) of the trial. At week 176 (3.4 years), the percentage loss in body weight was significantly higher in the three tirzepatide groups (−12.3%, –18.7%, and –19.7%) compared with placebo (−1.3%). Patients who received tirzepatide at any dose were significantly less likely to be diagnosed with type 2 diabetes during the treatment period (1.3% vs 13.3%; P < .001; NNT = 8).