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American Association of Clinical Endocrinology Annual Meeting
May 30, 2012
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Combination linagliptin, metformin suitable treatment option for type 2 diabetes

PHILADELPHIA — Treatment with combination linagliptin and metformin bested metformin alone in patients with type 2 diabetes, according to data presented at the American Association of Clinical Endocrinologists 21st Annual Scientific and Clinical Congress Meeting.

In an extension study, Maximilian von Eynatten, MD, global senior medical director of Boehringer Ingelheim, and colleagues conducted a 1-year, randomized, double blind extension study of a previous 6-month randomized, controlled trial.

The 6-month trial included six treatment groups:

  • Linagliptin 2.5 mg and metformin 500 mg twice daily.
  • Linagliptin 2.5 mg and metformin 1,000 mg twice daily.
  • Metformin 1,000 mg twice daily.
  • Metformin 500 mg twice daily.
  • Linagliptin 5 mg once daily.
  • Placebo.

In the extension study, 333 patients in the first three groups continued their respective treatment regimens. All other patients were randomly assigned to one of the three remaining groups (n=233).

“Numerically, the low-dose combination of linagliptin and metformin was as good as metformin alone, but the higher-dose combination was superior after 18 months of treatment, as compared with high-dose metformin,” Eynatten said during a presentation.

The average changes in HbA1c in the study during 1.5 years were:

  • –1.63% in the linagliptin 2.5 mg and metformin 1,000 mg twice daily group.
  • –1.32% in the linagliptin 2.5 mg and metformin 500 mg twice daily group.
  • –1.25% in the metformin 1,000 mg twice daily group.

“Metformin along brings 35% of patients to target after 6 months. Interestingly enough, this number seems to increase after 18 months. What happens here is the metformin arm loses about 25% [of patients] to rescue therapy. It’s a little bit misleading or gives the impression that metformin has a continuous effect,” Eynatten said.

According to data in the extension study, rescue medication usage was lower for the linagliptin 2.5 mg and metformin 1,000 twice daily group (14%), than in the linagliptin 2.5 mg and metformin 500 mg twice daily (27.6%) and metformin 1,000 mg twice daily (24.7%) groups.

“The initial combination of linagliptin and metformin was tolerated very well over a time period of 18 months, with low risk of hypoglycemia, and improved glycemic control better than the high dose of metformin alone,” Eynatten said.

For more information:

Eynatten MV. Abstract #1326. Presented at: the American Association of Clinical Endocrinologists 21st Annual Scientific and Clinical Congress Meeting; May 23-27, 2012; Philadelphia.

Disclosure:  Dr. von Eynatten is global senior medical director of Boehringer Ingelheim.

Perspective

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Harold E. Bays, MD, FACP, FACE, FNLA
Harold E. Bays, MD, FACP, FACE, FNLA

Von Eynatten et al reported the results of 1-year, randomized, double blind extension study of a previous 6-month, randomized, placebo-controlled trial of linagliptin combined with low- or high-dose metformin in patients with type 2 diabetes. Combined linagliptin (a dipeptidyl peptidase 4 or DPP-4 inhibitor) and metformin produced better long-term improvements in glycemic control vs. metformin alone.

The use of rescue medication was lower for the higher dose linagliptin/metformin combination groups, compared with the lower dose linagliptin/metformin groups and metformin monotherapy group.  Hypoglycemia ranged from approximately 3% to 6% among treatment groups. 

Usually, the main utility of an extension study is to assess safety, given that most extension studies are open-label. However, the extension phase of this study was double blinded, which better allows for some efficacy analyses. Importantly, no treatment group experienced clinically meaningful change in body weight or waist circumference.

This is important because many anti-diabetes medications increase body weight. Weight and waist circumference data may be especially important here because metformin is known to have beneficial effects upon adiposopathy (e.g. neutral or decreased visceral adiposity, decreased circulating free fatty acids, possible decreased leptin, increased adiponectin and decreased androgens in women).

Similarly, possibly related to DPP-4 being an adipokine, DPP-4 inhibitors may also favorably affect adiposopathy through reducing adipocyte size, decreasing visceral fat, improving insulin sensitivity, reducing adipose tissue inflammation, with some of these effects possibly being independent of GLP-1 effects. Effects like these may help explain the long-term efficacy of this combination.

Harold E. Bays, MD, FACP, FACE, FNLA
Medical Director / President
Louisville Metabolic and Atherosclerosis Research Center
Disclosures: Dr. Bays has received research grants and served as a consultant and speaker for numerous pharmaceutical companies.