Objective: Over 99% of the EMPA-REG OUTCOME trial participants had established cardiovascular disease (CVD). We aimed to investigate effectiveness and safety outcomes among patients with type 2 diabetes (T2D) initiating empagliflozin vs dipeptidyl peptidase-4 inhibitor (DPP-4i) across the broad spectrum of cardiovascular risk.

Methods: In a population-based cohort study we identified 39,072 pairs of 1:1 propensityscore-matched adult patients with type 2 diabetes (T2D) initiating empagliflozin or dipeptidyl peptidase-4 inhibitor (DPP-4i), using data from 2 U.S. commercial insurance databases and Medicare between 08/2014–09/2017. Primary outcomes were a composite of myocardial infarction (MI)/stroke, and hospitalization for heart failure (HHF). Safety outcomes were bone fractures, lower-limb amputations (LLA), diabetic ketoacidosis (DKA),and acute kidney injury (AKI). We estimated pooled hazard ratios (HR) and 95% CI adjusting for >140 baseline covariates.

Results: Study participants had mean age of 60 years and only 28% had established cardiovascular disease (CVD). Compared to dipeptidyl peptidase-4 inhibitor (DPP-4i), empagliflozin was associated with similar risk of myocardial infarction (MI)/stroke [HR (95% CI), 0.99 (0.81–1.21)], and lower risk of hospitalization for heart failure (HHF) [0.48 (0.35–0.67) and 0.63 (0.54–0.74), based on a primary and any heart failure HF discharge diagnosis, respectively]. The heart failure HF was 0.52 (0.38–0.72) for all-cause mortality (ACM) and 0.83 (0.70–0.98) for a composite of myocardial infarction MI/stroke/ all-cause mortality ACM. Empagliflozin was associated with a similar risk of lower-limb amputations LLA and fractures, an increased risk of diabetic ketoacidosis DKA [1.71 (1.08–2.71)], and a decreased risk of acute kidney injury AKI [0.60 (0.43–0.85)].
Conclusions: In clinical practice, the initiation of empagliflozin vs dipeptidyl peptidase-4 inhibitor DPP-4i was associated with a lower risk of hospitalization for heart failure (HHF), all-cause mortality (ACM), and myocardial infarction (MI)/stroke/ all-cause mortality (ACM),a similar risk of myocardial infarction (MI)/stroke, and a safety profile consistent with documented information.

Introduction: Diabetes mellitus (DM) is a chronic metabolic disorder marked by persistent hyperglycemia. While HbA1c has traditionally been used to assess glycemic control, growing evidence highlights glycemic variability (GV) and Time in Range (TIR) as more precise indicators of glucose fluctuations, which are linked to diabetic complications, especially chronic kidney disease (CKD). Emerging combination therapies targeting different pathophysiologic mechanisms of type 2 diabetes mellitus (T2DM), such as Sodium-glucose cotransporter (SGLT) 2 inhibitors and dipeptidylpeptidase (DPP)-4 inhibitors, offer promise in reducing glycemic variability.

Objective: To compare the efficacy of three commonly prescribed fixed-dose combination (FDC) therapies— Teneligliptin + Dapagliflozin (Arm-A), Sitagliptin + Dapagliflozin (Arm-B), and Linagliptin + Empagliflozin (Arm-C)—in improving glycemic control and renal parameters in Indian type 2 diabetes mellitus (T2DM) patients using continuous glucose monitoring (CGM).

Method: This prospective, comparative study enrolled 90 patients (30 in each arm). continuous glucose monitoring (CGM) was used to evaluate glycemic parameters including time-in-range [TIR], Time Above Range [TAR]), Time Below Range [TBR], Mean Amplitude of Glycemic Excursions (MAGE), Largest Amplitude of Glycemic Excursions (LAGE), Meanpost-prandial glycemic excursions (MPPGE), HbA1c, FPG, PPG, and renal function indicators (eGFR, serum creatinine, BUN) at baseline and study conclusion.

Results: All arms demonstrated significant improvements in time-in-range [TIR], MeanAmplitude of Glycemic Excursions (MAGE), Largest Amplitude of Glycemic Excursions (LAGE), HbA1c, FPG, and PPG (p<0.001). Arm-A showed a significantly superior reduction in Time Above Range [TAR]) and Mean post-prandial glycemic excursions (MPPGE) compared to Arm-B (p=0.029 and p=0.040, respectively)

Background: Sodium-glucose cotransporter (SGLT) 2 inhibitors attenuate fasting glomerular hyperfiltration in people with type 2 diabetes (T2D). However, Sodium-glucosecotransporter 2-inhibition increases glucagon levels, which facilitate postprandial hyperfiltration. The impact of Sodium-glucose cotransporter 2 inhibition on protein-related hyperfiltration and postprandial (intra) kidney haemodynamic function is unclear. Moreover, the interaction with dipeptidylpeptidase (DPP)-4 inhibitors, known to reduce glucagon levels and to affect meal related factors modulating glomerular filtration rate GFR, is unknown.
Aims: We aimed to assess the effects of empagliflozin and linagliptin in mono- and combination therapy compared to the initiation and intensification of SU-derivative gliclazide treatment on fasting and postprandial kidney haemodynamic function.
Materials and Methods: We compared three 16-week glucose-loweringstrategies added to ongoing metformin monotherapy: (1) EMPA-LINA: 8-week empagliflozin 10 mg QD (EMPA0-8w) followed by the addition of 8-week linagliptin 5 mg QD (LINA8-16w); (2) LINA-EMPA: 8-week linagliptin (LINA0-8w) followed by the addition of 8-week empagliflozin (EMPA8-16w) versus; (3) GLIC-GLIC: 8-week gliclazide 30 mg QD (GLIC0-8w) followed by the addition of 8-week gliclazide 30 mg (GLIC8- 16w). We studied (intra) kidney haemodynamic interactions of this combination using iohexol and PAHclearance techniques to assess measured glomerular filtration rate (mGFR) and effectiverenal plasma flow (ERPF).

Results: We studied n = 61 overweight people with type 2 diabetes T2D (HbA1c 62 + 11 mmol/mol, eGFR 89 [78_100] mL/min/1.73 m2 and urinary albumin-creatinine-ratio 1.0 [0.4_1.9] mg/mmol). In the fasting state, 0-8 week empagliflozin EMPA0-8w (−13.2; −21.3 to −5.1 mL/min) but not 0-8 week linagliptin LINA0-8w reduced within-group measured glomerular filtration rate (mGFR). 8-16 week empagliflozin EMPA8-16w (−10.2; −16.5 to −4.0 mL/min) but not 8-16 week linagliptin LINA8-16w reduced within-group measuredglomerular filtration rate (mGFR). Following a proteinload, 0-8 week empagliflozin EMPA0 8w (−11.4; −20.2 to −2.6 mL/min) and 8-16 week empagliflozin EMPA8-16w (−16.2; −22.9 to −9.4 mL/min) but not 0-8 week linagliptin LINA0-8wor 8-16 week linagliptin LINA8-16w reduced within-group measured glomerular filtrationrate (mGFR). Versus the comparatorarm, fasting measured glomerular filtration rate (mGFR) 0-8 week empagliflozin EMPA0-8w, 8-16 week empagliflozin EMPA8-16w and EMPA-LINA and postprandial mGFR EMPA8-16w and LINA-EMPA, were significantly reduced. measured glomerular filtration rate (mGFR) reductions resulted from intra kidney efferentvasodilation rather than afferent vasoconstriction.

Conclusion: In type 2 diabetes people without chronic kidney disease (CKD), the favourablekidney haemodynamic effects of empagliflozin persist in the postprandial state and are irrespective of concurrent use of linagliptin.