Adding Linagliptin to Basal Insulin Reduces Hypoglycemia in Older Patients with Type 2 Diabetes

DPP-4 inhibition noninferior to glimepiride in HbA1c reduction, with less hypoglycemia
August 2013, Vol 6 ADA 2013 Highlights
Mary Mosley

Chicago, IL—Hypoglycemia is a serious concern in elderly patients with type 2 diabetes who often require insulin therapy. Two new analyses presented as late-breaking posters at the 2013 American Diabetes Association annual meeting showed that adding linagliptin to basal insulin in elderly patients reduces the incidence of hypoglycemia in diabetic patients.

Reduced Hypoglycemia in Elderly Patients
The first study was presented by lead investigator Silvio E. Inzucchi, MD, Clinical Director of the Section of Endocrinology and Metabolism, Yale University, New Haven, CT. This exploratory analysis of data from 2 phase 3 trials included 247 elderly patients (mean age, 74 years) with type 2 diabetes, showing a 37% lower incidence of overall hypoglycemia (as defined by investigator) and a 34% lower incidence of confirmed hypoglycemia (blood glucose ≤70 mg/dL) when the oral dipeptidyl peptidase (DPP)-4 inhibitor linagliptin (Tradjenta) 5 mg daily was added to their basal insulin compared with placebo.

The reduced risk of hypoglycemia with linagliptin was observed in addition to a significant reduction at 24 weeks from baseline in hemoglobin (Hb) A1c levels. The baseline insulin dose was 36 U daily, with little change during the studies. HbA1c was reduced by –0.77% with linagliptin compared with placebo, from mean baseline levels of 8.2%. In patients with a baseline HbA1c <7.5%, a similar trend was seen, with a 23% reduction in the incidence of hypoglycemia.

“These new data, while highly preliminary, suggest that DPP-4 inhibition may somehow affect hypoglycemia rates in elderly patients managed with insulin,” said Dr Inzucchi. “This is obviously of clinical importance, given the detrimental effects, especially in an older patient group, of hypoglycemia. Possible explanations include improved glucagon secretory dynamics at the level of the pancreatic alpha-cell, but this is obviously conjecture at this point. This signal needs to be confirmed by others in larger studies,” Dr Inzucchi added.

The investigators noted that the finding of a reduction in hypoglycemic risk in concert with a reduction in HbA1c was “in stark contrast” to results seen with other oral agents in combination with insulin therapy.

Comparing Glimepiride and Linagliptin
Another late-breaking poster presented an exploratory analysis of the 2-year data from a phase 3 study that compared the benefit of DPP-4 inhibition with linagliptin 5 mg daily (N = 764) and the sulfonylurea glimepiride 1 mg to 4 mg daily (N = 755) in patients with hypoglycemia who received the sulfonylurea metformin. Hypoglycemia is common in patients with type 2 diabetes who are receiving a sulfonylurea.

In this study, Baptist Gallwitz, MD, of the Department of Medicine IV, Eberhard Karls Universität Tübingen, Germany, and colleagues, compared the use of linagliptin with glimepiride in patients with uncontrolled hypoglycemia who received metformin therapy.

The incidence of hypoglycemia (investigator-defined) was significantly reduced with linagliptin compared with glimepiride (7.5% vs 36.1%, respectively; P <.001). A significant difference in hypoglycemia incidence remained after excluding the events that occurred during dose escalation of glimepiride (25.8% compared with 5.9% with linagliptin).

Linagliptin outperformed glimepiride at reducing the risk of hypoglycemia at all time intervals examined up to 2 years, at all doses, at any age, and at level of change in HbA1c from baseline. The results of this study drive home the point that linagliptin provides noninferior reductions in HbA1c levels compared with glimepiride, but with the additional benefits of a lower risk for hypoglycemia and cardiovascular events, and without weight gain.

The investigators noted that this analysis “adds to the body of evidence that informs clinical decision-making for second-line treatment on top of metformin” in this new era of a more patient-focused approach to diabetes treatment.

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Last modified: October 7, 2013
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