Implications and Economic Impact of Applying International Guidelines and Recommendations to the Management of High-Risk Group of Type 2 Diabetes Mellitus Patients in India.

Objectives Sodium-glucose cotransporter-2 (SGLT-2) inhibitors and dipeptidyl peptidase IV (DPP-IV) inhibitors are recommended as preferred add-on oral antidiabetic drugs (OADs) after metformin among type 2 diabetes mellitus (T2DM) patients with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD). They are generally many folds costlier than other OADs. This is a simulatory analysis to assess the incremental cost escalation and risk reduction with their hypothetical substitution/addition in prescriptions of high-risk patients. Methods A simple simulation of cost-effectiveness analysis was performed using prescriptions of T2DM patients with established cardiovascular (CV) or renal disease or high-risk factors. SGLT-2 and DPP-IV inhibitors with proven benefits/safety were substituted or added in place of other OADs. Increments in treatment costs were calculated, and the anticipated decrease in hazards was extrapolated from cardiovascular outcome trials (CVOTs) and real-world studies. The incremental cost-effectiveness ratios (ICERs) were calculated. Results Prescriptions of 351 patients with a mean age of 58.04 ± 8.67 years were analyzed. The median annual acquisition cost of drug therapy for diabetes per patient was found to be Indian national rupee (INR) 8,964.4 for the original prescriptions when calculated using median retail prices of drugs prescribed for diabetes. Upon substituting one of the SGLT-2 inhibitors for the other OADs in the regimen, the cost increased to INR 12,265 (increase by 36.8%) for dapagliflozin, and INR 26,718 and INR 29,419 (increase by ~200%), respectively, for canagliflozin and empagliflozin. Upon calculating the ICERs, additional cost to prevent one all-cause death with dapagliflozin substitution is INR 660,020-25,384,369; INR 2,223,326 with empagliflozin substitution and INR 8,069,818 with canagliflozin substitution. The ICER for prevention of hospitalization with HF with dapagliflozin substitution is INR 1,320,040-1,435,543; INR 4,010,706 with empagliflozin and INR 5,548,000 with canagliflozin. To prevent a three-point major adverse cardiac event (3P-MACE), INR 2,062,562 would be needed with dapagliflozin substitution, and INR 3,146,861 and INR 3,859,478 with empagliflozin and canagliflozin, respectively. Incremental costs for various outcomes were higher with the addition of SGLT-2 inhibitors and significantly more if substitution with sitagliptin/linagliptin was also done. The numbers needed to treat were calculated too and ranged from 35 to 1,831 for various outcomes and drugs. Conclusion While the recommendations for use of SGLT-2 and DPP-IV inhibitors are adequately backed by evidence from CVOTs and real-world data, the incremental costs per event reduction are quite high for most outcomes in the Indian context. Dapagliflozin, being available as cheaper generic versions, appears to be most effective for most outcomes. Interpretations are subjective in terms of value assigned for preventing a major event.