An analysis of DPV and DIVE registry patients with chronic kidney disease according to the finerenone phase III clinical trial selection criteria.

BACKGROUND: The FIDELIO-DKD and FIGARO-DKD randomized clinical trials (RCTs) showed finerenone, a novel non-steroidal mineralocorticoid receptor antagonist (MRA), reduced the risk of renal and cardiovascular events in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Using RCT inclusion and exclusion criteria, we analyzed the RCT coverage for patients with T2DM and CKD in routine clinical practice in Germany. METHODS: German patients from the DPV/DIVE registries who were ≥ 18 years, had T2DM and CKD (an estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 OR eGFR ≥ 60 mL/min/1.73m2 and albuminuria [≥ 30 mg/g]) were included. RCT inclusion and exclusion criteria were then applied, and the characteristics of the two populations compared. RESULTS: Overall, 65,168 patients with T2DM and CKD were identified from DPV/DIVE. Key findings were (1) Registry patients with CKD were older, less often male, and had a lower eGFR, but more were normoalbuminuric vs the RCTs. Cardiovascular disease burden was higher in the RCTs; diabetic neuropathy, lipid metabolism disorders, and peripheral arterial disease were more frequent in the registry. CKD-specific drugs (e.g., angiotensin-converting enzyme inhibitors [ACEi] and angiotensin receptor blocker [ARBs]) were used less often in clinical practice; (2) Due to the RCT's albuminuric G1/2 to G4 CKD focus, they did not cover 28,147 (43.2%) normoalbuminuric registry patients, 4,519 (6.9%) albuminuric patients with eGFR < 25, and 6,565 (10.1%) patients with microalbuminuria but normal GFR (≥ 90 ml/min); 3) As RCTs required baseline ACEi or ARB treatment, the number of comparable registry patients was reduced to 28,359. Of these, only 12,322 (43.5%) registry patients fulfilled all trial inclusion and exclusion criteria. Registry patients that would have been eligible for the RCTs were more often male, had higher eGFR values, higher rates of albuminuria, more received metformin, and more SGLT-2 inhibitors than patients that would not be eligible. CONCLUSIONS: Certain patient subgroups, especially non-albuminuric CKD-patients, were not included in the RCTs. Although recommended by guidelines, there was an undertreatment of CKD-patients with renin-angiotensin system (RAS) blockers. Further research into patients with normoalbuminuric CKD and a wider prescription of RAS blocking agents for CKD patients in clinical practice appears warranted.

Comparing diabetes due to diseases of the exocrine pancreas to type 1 and type 2 diabetes using propensity score matching.

OBJECTIVE: To estimate the prevalence of diabetes due to diseases of the exocrine pancreas (DEP) using data of the multicentre diabetes patient follow-up registry. Moreover, we aimed at comparing individuals with diabetes due to DEP to individuals with type 1 and type 2 diabetes. METHODS: Individuals with DEP, type 1 or type 2 diabetes ≥18 years of age were studied. We aggregated the most recent treatment year per patient and used propensity scores to match diabetes due to DEP to type 1 and type 2 diabetes. Matching was conducted one-to-one with sex, age, diabetes duration, migration background and the German index of socioeconomic deprivation as covariates. RESULTS: We identified 7,093 (1.6%) individuals with diabetes due to DEP. In the matched cohort DEP-type 1 diabetes we observed a similar daily insulin dose (0.62 IU/kg (95% confidence interval:0.60-0.63), 0.60 IU/kg (0.58-0.62)) and significant differences regarding microvascular (41.0% (39.7-42.2), 45.3% (44.0-46.6)), and macrovascular disease (16.6% (15.7-17.6), 14.7% (13.8-15.6)). HbA1c (8.2% (8.1-8.3), 7.9% (7.8-8.0)), daily insulin dose (0.60 IU/kg (0.58-0.62), 0.56 IU/kg (0.54-0.58)) and event rates of severe hypoglycemia (23.9 events/100 PY (21.4-26.8), (9.5 events/100 PY (8.0-11.2)) were significantly higher in individuals with diabetes due to DEP compared to type 2 diabetes. CONCLUSIONS: Using registry data, rare diabetes types such as diabetes due to DEP can be studied with a significant sample size. Our study identified differences and similarities between adult individuals with DEP related diabetes and type 1 or type 2 diabetes.

Exenatide twice daily versus premixed insulin aspart 70/30 in metformin-treated patients with type 2 diabetes: a randomized 26-week study on glycemic control and hypoglycemia.

OBJECTIVE: Hypoglycemia causes recurrent morbidity in patients with type 2 diabetes. This study evaluated if exenatide twice daily (BID) was noninferior to premixed insulin aspart 70/30 BID (PIA) for glycemic control and associated with less hypoglycemia. RESEARCH DESIGN AND METHODS: In this open-label study, metformin-treated adults with type 2 diabetes were randomized to 26-week treatment with exenatide BID (4 weeks 5 µg, then 10 µg) or PIA. RESULTS: Exenatide BID (n = 181) was noninferior to PIA (n = 173) for A1C control (least squares [LS] mean change -1.0 vs. -1.14%; difference [95% CI] 0.14 [-0.003 to 0.291]) and associated with a lower risk for hypoglycemia (8.0 vs. 20.5%, P < 0.05). LS mean weight decreased by 4.1 kg and increased by 1.0 kg with PIA (P < 0.001). A total of 39.2 vs. 20.8% of patients reached the composite end point of A1C <7.0%, no weight gain, and no hypoglycemia (P < 0.001; post hoc analysis). CONCLUSIONS: In metformin-treated patients, exenatide BID was noninferior to PIA for glycemic control but superior for hypoglycemia and weight control.