Cardiovascular outcomes and safety with linagliptin, a dipeptidyl peptidase-4 inhibitor, compared with the sulphonylurea glimepiride in older people with type 2 diabetes: A subgroup analysis of the randomized CAROLINA trial

Mark A. Espeland, Richard E. Pratley, Julio Rosenstock, Takashi Kadowaki, Yutaka Seino, Bernard Zinman, Nikolaus Marx, Darren K. McGuire, Knut Robert Andersen, Michaela Mattheus, Annett Keller, Maria Weber, Odd Erik Johansen

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1 Scopus citations

Abstract

Aim: To compare the cardiovascular (CV) safety of linagliptin with glimepiride in older and younger participants in the CAROLINA trial in both prespecified and post hoc analyses. Materials and Methods: People aged 40 to 85 years with relatively early type 2 diabetes, inadequate glycaemic control and elevated CV risk were randomly assigned to linagliptin 5 mg or glimepiride 1 to 4 mg. The primary endpoint was time to first occurrence of three-point major adverse CV events (MACE: CV death, non-fatal myocardial infarction, or non-fatal stroke). We evaluated clinical and safety outcomes across age groups. Results: Of 6033 participants, 50.7% were aged <65 years, 35.3% were aged 65 to 74 years, and 14.0% were aged ≥75 years. During the 6.3-year median follow-up, CV/mortality outcomes did not differ between linagliptin and glimepiride overall (hazard ratio [HR] for three-point MACE 0.98, 95.47% confidence interval [CI] 0.84, 1.14) or across age groups (interaction P >0.05). Between treatment groups, reductions in glycated haemoglobin were comparable across age groups but moderate-to-severe hypoglycaemia was markedly reduced with linagliptin (HR 0.18, 95% CI 0.15, 0.21) with no differences among age groups (P = 0.23). Mean weight was −1.54 kg (95% CI –1.80, –1.28) lower for linagliptin versus glimepiride. Adverse events increased with age, but were generally balanced between treatment groups. Significantly fewer falls or fractures occurred with linagliptin. Conclusions: Linagliptin and glimepiride were comparable for CV/mortality outcomes across age groups. Linagliptin had significantly lower risk of hypoglycaemia and falls or fractures than glimepiride, including in “older-old” individuals for whom these are particularly important treatment considerations.

Original languageEnglish (US)
Pages (from-to)569-580
Number of pages12
JournalDiabetes, Obesity and Metabolism
Volume23
Issue number2
DOIs
StatePublished - Feb 2021

Keywords

  • DPP-4 inhibitor
  • cardiovascular disease
  • clinical trial
  • hypoglycaemia
  • linagliptin
  • sulphonylureas

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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