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Napp brings you recent and clinically relevant publications in the evolving field of Type 2 diabetes recommended by an international panel of specialists.
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Dr. Patrick Holmes

General Practitioner, St. George's Medical Practice, Darlington, UK

Dr. Juan José Gorgojo Martínez Image
Dr. Juan José Gorgojo Martínez

Head of Department of Endocrinology and Nutrition, University Hospital Fundación, Alcorcon, Madrid, Spain

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Dr. Salvatore A. De Cosmo

Head of Unit of Internal Medicine and Endocrinology, Scientific Institute "Casa Sollievo della Sofferenza" San Giovanni Rotondo, Italy

SURPASS-1: tirzepatide vs. placebo

Novel dual GIP and GLP-1 receptor agonist tirzepatide as monotherapy in T2DM demonstrated clinically significant reductions in HbA1c and bodyweight without increased risk of clinically significant or severe hypoglycaemia vs placebo in the SURPASS-1 trial.

Tirzepatide is a novel once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist.

SURPASS-1 assessed the glycaemic efficacy and safety of tirzepatide in people with type 2 diabetes (T2DM) inadequately controlled with diet and exercise alone. In this double-blind phase 3 study, people with T2DM (N=478; mean baseline HbA1c 7.94%; age 54.1 years; disease duration 4.7 years) were randomised (1:1:1:1) to tirzepatide (5, 10, 15 mg once weekly) or placebo.

Primary efficacy measure was mean change in HbA1c from baseline. At 40 weeks, all tirzepatide doses were superior to placebo for changes from baseline in HbA1c, as well as in secondary endpoints of change in fasting serum glucose, meaningful bodyweight loss, and proportion achieving HbA1c targets. Specifically,

  • Mean HbA1c decreased from baseline by 1.87% with tirzepatide 5 mg, 1.89% with tirzepatide 10 mg, and 2.07% with tirzepatide 15 mg versus +0.04% with placebo
  • Tirzepatide induced a dose-dependent bodyweight loss ranging from 7.0 to 9.5 kg
  • 87-92% participants given tirzepatide reached HbA1c < 7%, versus 20% on placebo
  • Also notably, among those receiving tirzepatide 15 mg, 52% achieved normoglycaemia (HbA1c < 5.7%) and 27% achieved ≥ 15% bodyweight loss

The safety profile was consistent with GLP-1 receptor agonists. The most frequent adverse events with tirzepatide were mild to moderate and transient gastrointestinal events, including nausea (12-18% vs 6% placebo), diarrhoea (12-14% vs 8% placebo), and vomiting (2-6% vs 2% placebo). No clinically significant (< 54 mg/dL [< 3 mmol/L]) or severe hypoglycaemia were reported with tirzepatide.

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