Endocrine Abstracts

Introduction: There is always been a need for safe and effective adjuvant therapy in type 1 Diabetes not just for glycemic control but also for cardio-renal benefits.

Objectives: To evaluate whether addition of DPP-4 inhibitors reduces the ketogenic potential of SGLT2i when used as an adjuvant therapy in type 1 Diabetes.

Materials & Methods: 20 type 1 Diabetes subjects above 18 years of age with poorly controlled glycemia (HbA1c 7 to 10%) were included in the study. At baseline along with physical examination, biochemical parameters-FPG, PPG, HBA1C, beta-hydroxybutyrate and fasting Glucagon were collected. This cohort was then treated with sitagliptin for 3 months, dapagliflozin for 3 months and combination of sitagliptin and dapagliflozin for 3 month adjuvant to insulin. At the end of each 3 months period anthropometric and biochemical parameters were assessed.

Results & observation: The plasma Glucagon levels compared with the baseline (30.99pg/ml), did not change with sitagliptin (29.89 pg/ml), increased significantly with dapagliflozin (55.89pg/ml) [+24.9pg/ml (P<0.05)] and the combination treatment failed to reduce the Glucagon level 49.37pg/ml. The median ketone (beta-hydroxybutyrate) levels compared to the baseline [0.11(0.04 -0.87)] were numerically lower with sitagliptin [0.06(0.02 - 0.33)] and higher with dapagliflozin [0.14(0.04 - 1.16)]. However, the combination treatment failed to reduce the ketone levels [0.17(0.02 - 0.92)]. There was a statistically significant improvement in glycemic parameter, HbA1c with each of the intervention. On comparing with the baseline the mean difference of HbA1c after sitagliptin was 1.39%, after dapagliflozin was 1.08% and after the combination treatment was 1.59%. This was achieved with no change in the insulin dose. There was a reduction in weight, BMI, SBP and DBP with individual as well as combination treatment. Change in waist circumference was minimal.

Conclusions: Sitagliptin and dapagliflozin either alone or in combination as adjuvant therapy in type 1 diabetes results in a significant improvement in glycaemia. Sitagliptin failed to reduce fasting plasma glucagon and blood ketone (beta-hydroxybutyrate) levels when added to dapagliflozin. It thus appears that the ketogenic potential of dapagliflozin cannot be brought down by addition of sitagliptin. Thus, DPP4 inhibitors and SGLT2 inhibitors can be a useful adjuvant in the therapy of type 1 DM, but SGLT2 inhibitors should be used only after understanding the potential risk for ketosis.