New research assesses safety and efficacy of linagliptin as add on treatment in elderly diabetes patients….
Linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, can assist with lowering blood glucose by inhibiting the enzymes responsible for breaking down incretins (GLP-1 and GIP).
Researchers evaluated liagliptin to determine safety and efficacy of use as add on treatment to diabetes regimens in the elderly. The randomized, double-blinded, placebo controlled study looked at persons 70 years and older (mean age of 74.9 years) who had type 2 diabetes and were currently on metformin, sulfonylureas, basal insulin or a combo thereof, for at least 8 weeks and had inadequate blood glucose control defined as HbA1C of >7% (mean A1C = 7.8%). A total of 241 participants were included in the study, 162 in the linagliptin group and 79 in the placebo group. The patients had either 5mg of linagliptin or placebo added onto their existing regimen and were followed for 24 weeks. Changes to their pre-existing regimen were limited to after 12 weeks of treatment, then dosage changes were allowed. Patients demonstrating LFTs (AST/ALT/ALP) >3x upper limit of normal; patients on rapid acting, pre-mixed insulin or systemic corticosteroids; patients who had a MI, CVA or TIA within 3 months of study; patients treated with a thiazolidinedione, α-glucosidase inhibitor, meglitinide, GLP1 analogue, DPP4 inhibitor, or anti-obesity drug within 3 months of study start; patients with fasting plasma glucose (FPG) >133 and patients who had a previous bariatric surgery were excluded from the study.
The placebo-adjusted mean decrease of A1C in the linagliptin group was 0.64% (95% CI −0.81 to −0.48%, p<0·0001) after 24 weeks. And placebo-adjusted mean decrease in FPG from baseline was also significantly different between linagliptin group vs. placebo with mean FPG lower at each time point in the linagliptin group but higher in the placebo group (even though the study was powered for determining differences in A1C). Many of the patients included in the study did have co-morbidities but they were similar between treatment and placebo groups. Main comorbidities included renal disease, cardiovascular disease and polypharmacy. Adverse events did occur in both the treatment (linagliptin) and placebo groups, 21% vs. 13.9% respectively; serious adverse events, not drug related, occurred in 8.6% vs. 6.3% of the linagliptin vs. placebo groups. Hypoglycemic event occurrence was not significantly different between the groups.
The researchers concluded that linagliptin may be a safe add-on therapy for elderly patients who are experiencing difficulty with managing their type 2 diabetes. However, they also recommended close monitoring of these patients because many elderly patients have co-morbidities and because of the small sample size. Also, results indicated that 3.1% of patients in the linagliptin group vs. 0% of patients in the placebo group complained of vertigo. This may have been an event related to a confounding factor but because vertigo and falls in the elderly can be detrimental, the researchers recommended careful screening at follow-up visits to prevent any adverse outcomes.
- Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor blocks DPP, an enzyme responsible for breaking down intestinal incretins such as GLP-1 and GIP which can delay gastric emptying, decrease glucagon secretion and increase insulin secretion, and improve satiety response.
- Other DPP-4 inhibitors on the market are: sitagliptin, alogliptin, and saxagliptin.
- Linagliptin may be safe and effective as add on treatment for elderly patients who are not well controlled on current regimen for type 2 diabetes; study results show a similar safety profile as compared to placebo and improved glucose control as noted by a placebo-adjusted mean decrease of 0.64% in A1C.
Barnett, Anthony et al. Linagliptin for Patients aged 70 years or Older with Type 2 Diabetes Inadequately Controlled with Common Antidiabetes Treatments: A Randomised, Double-blind, Placebo-controlled Trial. Lancet 2013; 382: 1413–23