Linagliptin: Cardiovascular and Renal Safety beyond Doubt at a Steep Price

Dipeptidyl peptidase-IV inhibitors or “gliptins” are commonly used oral anti-diabetic drugs for Type 2 diabetes mellitus, preferred as add-on therapy after metformin. Various cardiovascular outcome trials (CVOTs) have established their cardiovascular safety. Approved later than other gliptins, linagliptin has unique pharmacokinetic profile. A literature review was performed by searching science databases, in addition to the Medline database via PubMed, for relevant articles. The search included meta-analyses, systematic reviews, review articles, and randomized and nonrandomized trials. Related publications in the English language were reviewed, and the most relevant papers were summarized. This review explores the potential of clinical use of this drug in light of the two recently reported CVOTs, and cost of therapy. Results of CAROLINA and CARMELINA, published in 2019 and 2018, respectively, provide robust proof of long-term CV and renal safety of linagliptin. Both trials are first of their kinds for including diabetes population with renal compromise and use of an active comparator, respectively. Physicians can confidently choose in subsets of adults with diabetes who have compromised renal or cardiac functions or who are at high risk without any dose adjustments. However, the price of the drug is very high, costlier than other oral drugs. Cost remains the biggest hurdle and is likely to remain so with the drug being patent protected for a considerable time in future. Thus, despite the promise of CV and renal safety, linagliptin is likely to remain out of reach for majority of the Indian population with diabetes.