A new analysis by Komodo Health, accepted at the American Diabetes Association annual conference, finds similar rates of hypoglycemia in patients treated with metformin as with DPP4I monotherapies.

As medicine evolves, the disruption of long-standing treatment protocols by novel therapeutics creates moments of both risk and opportunity. Diabetes is one of the largest therapeutic landscapes to see recent change. As one of the most common diseases in the U.S. — diabetes affects over 37 million people, or 11% of the population — any improvements to available treatments have a high potential for impact.

Hypoglycemia, or low blood sugar, is one complication of treatments for diabetes. And minimizing the risk of hypoglycemia is a cornerstone of the prevention of the number one cause of death in people living with diabetes — cardiovascular disease. For the past 20 years, metformin monotherapy has been the most common first-line therapy for hyperglycemia, or high blood sugar, in patients with diabetes. With so many Americans affected by this disease, researchers, pharmacology professionals, and physicians alike are motivated to get the most effective and up-to-date treatments to patients, leading to the development of new therapeutics and treatment approaches in the market.

In recent years, DPP-4 inhibitors (DPP4Is) have gained popularity among treating physicians for use as a first-line therapy for hyperglycemia in patients with diabetes. The mechanisms of action of DPP4Is are different from metformin, which acts primarily by reducing glucose produced in the liver and by increasing insulin sensitivity. DPP4Is act primarily by stimulating insulin production. However, it has been unclear whether this new class of drugs is superior to metformin in treating hyperglycemia without increasing the risk of complications such as hypoglycemia. 

We explored this question in a Komodo Health poster that was recently accepted to the American Diabetes Association annual conference. Using U.S. closed claims data from Komodo’s Healthcare Map™, we compared the incidence of hypoglycemia in patients with diabetes taking single-gradient metformin monotherapy with those taking a DPP4I monotherapy. Over 2 million patients on metformin were included alongside 45,400 patients on a DPP4I.

Patients with at least 18 months of continuous enrollment between 2016 and 2020 were included, with 12 months prior to and six months following their first prescription of metformin or DPP4I. Patients should not have received any anti-diabetes treatment within the year before their first prescription. The two groups were compared on several variables, including age, gender, location, medication adherence, emergency department visits, and various measures of comorbidity. Propensity score matching was then used to match the 45,400 patients in the DPP4I group to the metformin group, and incidence rates of hypoglycemia were compared. 

Significant differences in patient demographics were seen across therapeutic groups. 
Patients on monotherapy DPP4I were older, on average, than those on metformin (a mean of 64 vs. 50, respectively) and were more likely to have chronic kidney disease (28% vs. 4%). Patients in the DPP4I group had more comorbidities and associated risk by the Charlson Comorbidity Index (CCI). A CCI score considered “severe” was seen in 54% of patients in the DPP4I group but in only 16% of the metformin group. Similar medication adherence rates were seen across both groups.

Patients taking DPP4Is were 14% more likely to experience hypoglycemia than those taking metformin, although this was of borderline significance. 
After patients were matched for demographic variables, comorbidities, and adherence, a similar rate of hypoglycemia was found in both groups — 19.17 in the DPP4I group, compared with 16.82 in the metformin group. This suggests that the higher number of hypoglycemia episodes initially seen in the DPP4I group were likely related more to the patient population being slightly older and sicker. It also suggests that the sizable risk of hypoglycemia in patients treated with DPP4Is should be considered while managing diabetes while minimizing risks of cardiovascular disease in patients.

The insights from this rigorous analysis can act to support and inform prescription decision-making among clinicians navigating a shifting landscape of therapeutic options for their diabetic patients. The duration of this analysis, paired with its additional depth and visibility into demographics, past medical history, and subsequent complications, highlights Komodo Health’s capacity to generate medical-grade findings that have been previously unavailable. Our full-stack software suite built atop our Healthcare Map provides a unique opportunity to access a higher volume of cleaned, longitudinal, closed claims patient data for analyses, as highlighted in this analysis, to generate insights that support our mission of reducing the burden of disease.

Read the poster: .

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