Koichi Hirao

Insulin degludec/insulin aspart versus biphasic insulin aspart 30 in Asian patients with type 2 diabetes inadequately controlled on basal or pre-/self-mixed insulin: A 26-week, randomised, treat-to-target trial

AIMSnInsulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of IDeg and IAsp. This pan-Asian, 26-week trial investigated efficacy and safety of IDegAsp vs biphasic insulin aspart 30 (BIAsp 30) in Asian adults with type 2 diabetes (T2DM), inadequately controlled on once- or twice-daily (BID) basal, premixed or self-mixed insulin.nnnMETHODSnParticipants (mean age 59.8 years, HbA1c 8.4%, FPG 7.9 mmol/L, BMI 25.4 kg/m(2)) were randomised 2:1 to BID IDegAsp (n=282) or BIAsp 30 (n=142) and continued existing metformin treatment. Insulins were administered with breakfast and main evening meal, titrated to a pre-breakfast and pre-main evening meal self-measured plasma glucose target of 4-5 mmol/L.nnnRESULTSnIDegAsp achieved the primary endpoint of non-inferiority to BIAsp 30 for mean change in HbA₁c (estimated treatment difference [ETD] IDegAsp-BIAsp 30: 0.05% points [95% CI -0.10; 0.20]). IDegAsp was superior in lowering fasting plasma glucose (FPG) (ETD -1.06 mmol/L, 95% CI -1.43; -0.70, p<0.001), and resulted in a lower final mean daily insulin dose (0.79 U/kg vs 0.99 U/kg, estimated rate ratio [RR] 0.79, 95% CI 0.73; 0.85, p<0.0001). Rates of overall confirmed and severe hypoglycaemia were similar between treatments, while rate of nocturnal confirmed hypoglycaemia was numerically (p=ns) lower with IDegAsp. During the maintenance period there was a trend (p=ns) towards lower hypoglycaemia rates for IDegAsp.nnnCONCLUSIONnIn Asian adults with T2DM, IDegAsp BID effectively improves long-term glycaemic control, and compared to BIAsp 30, provides superior reductions in FPG with a lower dose, and numerically less nocturnal hypoglycaemia.

Chronic kidney disease categories and renal–cardiovascular outcomes in type 2 diabetes without prevalent cardiovascular disease: a prospective cohort study (JDDM25)

Aims/hypothesisIn type 2 diabetic patients at low risk for cardiovascular disease (CVD), the relationship between the clinical course of nephropathy by stage of chronic kidney disease (CKD) and onset of CVD remains unclear. Clarification of this relationship is important for clinical decision-making for both low- and high-risk diabetic patients.MethodsThis 4xa0year prospective study enrolled 2,954 type 2 diabetic patients with no prevalent CVD, and serum creatinine <176.8xa0μmol/l. The risk for CVD onset (non-fatal and fatal CVD and stroke, and peripheral arterial disease) was assessed according to CKD stage categorised by urinary albumin-to-creatinine ratio (ACR; mg/mmol) and estimated GFR (eGFR; mlxa0min−1 1.73xa0m−2). Association of progression from ‘no CKD’ stage (ACR <3.5xa0mg/mmol and eGFR ≥90xa0mlxa0min−1 1.73xa0m−2) with risk for CVD onset was also evaluated.ResultsDuring follow-up (median 3.8xa0years), 89 CVD events occurred. Compared with patients with ‘no CKD’ as reference, those with ACRu2009≥u200935.0xa0mg/mmol with co-existing eGFR 60–89xa0mlxa0min−1 1.73xa0m−2 or <60xa0mlxa0min−1 1.73xa0m−2 showed increased risk for CVD onset, whereas those with eGFR ≥90xa0mlxa0min−1 1.73xa0m−2 did not. Those with ACR <3.5xa0mg/mmol and eGFR <60xa0mlxa0min−1 1.73xa0m−2 did not show any increased risk. Among patients with ‘no CKD’ stage at baseline, those who progressed to ACR ≥3.5xa0mg/mmol during follow-up showed an increased risk compared with those who did not, whereas those who progressed to eGFR <90xa0mlxa0min−1 1.73xa0m−2 did not have increased risk.Conclusions/interpretationThe risk for CVD was associated with progression of albuminuria stage rather than eGFR stage in type 2 diabetic patients at relatively low risk for CVD.

Pioglitazone treatment and cardiovascular event and death in subjects with type 2 diabetes without established cardiovascular disease (JDDM 36).

AIMSnThe protective association of pioglitazone with cardiovascular events and death was investigated over 6-years in large-scale type 2 diabetic subjects without established cardiovascular disease in a primary care setting.nnnMETHODSnA six-year observational cohort study including 2864 subjects with type 2 diabetes without established cardiovascular disease was performed. The primary endpoint was a composite of first occurrence of cardiovascular disease or death. The effect of pioglitazone use at a baseline year with a Cox proportional hazard model and the time-dependent use in each one-year examination interval with a pooled logistic regression model were analyzed.nnnRESULTSnBaseline use of pioglitazone (n=493) did not show a statistically protective effect on the primary endpoint (n=175), although it tended to reduce the risk (adjusted hazard ratio 0.67 [95% CI: 0.43-1.05]). However, pooled logistic regression analysis indicated a significant protective association of pioglitazone with the primary endpoint (0.58 [0.38 to 0.87] and cardiovascular disease (0.54 [0.33-0.88]), independent of concurrent levels of blood glucose, blood pressure, lipids, albuminuria, and renal function. In particular, this protective association was observed in those with diabetic nephropathy regardless of the daily dose of pioglitazone. Among a total of 898 subjects who took pioglitazone during the period, 43% experienced a discontinuation at least once; however, serious adverse effects were rare.nnnCONCLUSIONSnThis observational study indicated a protective association of pioglitazone with cardiovascular disease and death in type 2 diabetic subjects without established vascular disease, particularly those with nephropathy.

The initiation of insulin therapy in type 2 diabetic patients treated with oral anti-diabetic drugs: an observational study in multiple institutes across Japan (JDDM27)

Introduction nWe examined the clinical characteristics of type 2 diabetes mellitus (T2D) patients requiring insulin therapy and evaluated the efficacy of adding insulin therapy regimens to oral anti-diabetic drugs.

Insulin degludec/insulin aspart versus biphasic insulin aspart 30 twice daily in insulin-experienced Japanese subjects with uncontrolled type 2 diabetes: Subgroup analysis of a Pan-Asian, treat-to-target Phase 3 Trial

The present study was a subgroup analysis of a Pan‐Asian Phase 3 open‐label randomized treat‐to‐target trial evaluating insulin degludec/insulin aspart (IDegAsp) and biphasic insulin aspart 30 (BIAsp 30) in Japanese subjects with type 2 diabetes inadequately controlled on insulin.