Differing effects of liraglutide on gastric emptying in Japanese patients with type 2 diabetes

This study was performed to clarify the influence of liraglutide on gastric emptying in Japanese patients with type 2 diabetes. In 16 patients, the [¹³C]‐acetate breath test was performed to compare gastric emptying before and after liraglutide treatment. We found two patterns of response, with gastric emptying being delayed by liraglutide in seven patients (delayers) and not delayed in nine patients (non‐delayers). The mean increase of the maximum gastric emptying time was 31 ± 4 min (p < 0.01 vs. baseline) in the delayers, while it was only 2 ± 3 min (p = 0.60 vs. baseline) in the non‐delayers. The delayers showed a greater early decrease of AUC‐PG from 0 to 60 min, despite no increase of the plasma insulin level compared with non‐delayers. In conclusion, the effect of liraglutide treatment on gastric emptying shows heterogeneity, and patients can be classified as delayers or non‐delayers.     

Safety and efficacy of vildagliptin versus placebo in patients with type 2 diabetes and moderate or severe renal impairment: a prospective 24-week randomized placebo-controlled trial

Aim: Assess safety/tolerability and efficacy of the DPP‐4 inhibitor vildagliptin in 515 patients with type 2 diabetes mellitus (T2DM) and moderate or severe renal impairment (RI). Methods: Double‐blind, randomized, parallel‐group, placebo‐controlled, 24‐week clinical trial assessing safety and efficacy of vildagliptin (50 mg qd) added to current antidiabetic therapy, in patients with T2DM and moderate or severe RI (GFR ≥ 30 to <50 or <30 ml/min/1.73 m²). Results: The study population comprised of 165 and 129 patients with moderate RI and 124 and 97 patients with severe RI randomized to vildagliptin and placebo, respectively, with most patients receiving background insulin therapy (68 and 81% for moderate and severe RI, respectively). After 24 weeks, the between‐treatment difference in the adjusted mean change in A1C was ?0.5 ± 0.1% (p < 0.0001) in moderate RI (baseline A1C = 7.9%) and ?0.6 ± 0.1% (p < 0.0001) in severe RI (baseline A1C = 7.7%). In patients with moderate RI, similar proportions of those receiving vildagliptin or placebo experienced any AE (68 vs. 73%), any SAE (9 vs. 9%), any AE leading to discontinuation (3 vs. 5%) or death (1 vs. 1%). This was also true for patients with severe RI: AEs (73 vs. 74%), SAEs (19 vs. 21%), AEs leading to discontinuation (9 vs. 6%) and death (2 vs. 4%). Conclusions: In this 24‐week study of 515 patients with T2DM and moderate or severe RI, vildagliptin added to ongoing antidiabetic therapy had a safety profile similar to placebo. Further, relative to placebo, vildagliptin elicited a statistically and clinically significant decrease in A1C in patients with moderate or severe RI.     

Prevalence and progression of chronic kidney disease among patients with type 2 diabetes: Insights from the DISCOVER study

We report the prevalence and change in severity of chronic kidney disease (CKD) in DISCOVER, a global, 3-year, prospective, observational study of patients with type 2 diabetes (T2D) initiating second-line glucose-lowering therapy. CKD stages were defined according to estimated glomerular filtration rate (eGFR). Overall, 7843 patients from 35 countries had a baseline serum creatinine measurement. Of these (56.7% male; mean age: 58.1 years; mean eGFR: 87.5 mL/min/1.73 m²), baseline prevalence estimates for stage 0-1, 2, 3 and 4-5 CKD were 51.4%, 37.7%, 9.4% and 1.4%, respectively. A total of 5819 patients (74.2%) also had at least one follow-up serum creatinine measurement (median time between measurements: 2.9 years, interquartile range: 1.9-3.0 years). Mean eGFR decreased slightly to 85.7 mL/min/1.73 m² over follow-up. CKD progression (increase of ≥1 stage) occurred in 15.7% of patients, and regression (decrease of ≥1 stage) in 12.0%. In summary, a substantial proportion of patients with T2D developed CKD or had CKD progression after the initiation of second-line therapy. Renal function should be regularly monitored in these patients, to ensure early CKD diagnosis and treatment.     

Fixed-ratio combination of insulin degludec and liraglutide (IDegLira) improves cardiovascular risk markers in patients with type 2 diabetes uncontrolled on basal insulin

In this post hoc analysis we investigated the effects of insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus comparators on cardiovascular (CV) risk markers in participants in the DUAL II (vs. insulin degludec), DUAL V (vs. insulin glargine 100 units/mL) and DUAL VII (vs. basal–bolus therapy) trials, grouped by sex, age (<65 years, ≥65 years) and diabetes duration (<10 years, ≥10 years). Treatment contrasts were in favour of IDegLira in many subgroups for changes from baseline in glycated haemoblogin (DUAL II, DUAL V), body weight (all three trials), systolic blood pressure (BP; all three trials), HDL cholesterol (DUAL VII) and LDL cholesterol (DUAL II, DUAL V). Higher heart rates were seen with IDegLira versus comparators (all three trials) plus significantly higher diastolic BP in men (DUAL V). Differences in treatment effect were seen between sexes in waist circumference (DUAL II), systolic BP (DUAL II, DUAL V) and triglycerides (DUAL VII), and between diabetes durations in LDL cholesterol (DUAL V). In conclusion, IDegLira is associated with a general improvement in CV risk markers compared with basal insulin or basal–bolus therapy after 26 weeks of treatment.     

A randomized controlled trial protocol of the cardiovascular safety and efficacy of liraglutide in the treatment of type 2 diabetes

Background:Recently, many clinical experiments have evaluated the influences of liraglutide in the treatment of type 2 diabetes. However, the outcomes of these studies are inconsistent, and the number of high-quality prospective trials that conducted to assess the cardiovascular safety is limited. Hence, for this research, it was implemented for the assessment of the cardiovascular effectiveness and safety of liraglutide in type 2 diabetes patients.Methods:This research was a 26-week active controlled and randomized trial. Our research protocol follows the guidelines of Good Clinical Practice issued via the Helsinki Declaration and International Conference on Coordination. All the patients will receive the written informed consent in order to involve in our clinical experiment. The participants with type 2 diabetes aged from 18 years to 80 years, patients with 45.0 kg/m² body-mass index or less, and with glycosylated hemoglobin of 7.5 to 10.0 percent, and received metformin (daily 1500 mg or more) for 3 months or longer were eligible. All the patients were randomized to 1 of 2 interventions (in the ratio of 1:1): liraglutide placebo once daily (blinded) and liraglutide once daily (blinded), respectively, both combined with the glimepiride and metformin (open-labeled). For the efficacy variable, the major endpoint was the baseline glycated hemoglobin change after treating for 26 weeks. The secondary end points involved: the percentage of participants who achieved the goals of postprandial blood glucose, fasting blood glucose, and glycosylated hemoglobin; the changes of mean postprandial blood glucose, fasting blood glucose, and the body weight, pancreatic B-cell function index, and changes in blood pressure and insulin resistance assessed by homeostasis model.Conclusions:For this research, the limitations involve the short trial period and the limitation of glimepiride in some countries, thus excluding the maximum doses of glimepiride.Trial registration:This study protocol was registered in Research Registry (researchregistry6306).     

Preventing microalbuminuria in patients with type 2 diabetes

The public health burden of type 2 diabetes mellitus has been dramatically increasing world-wide. The chronic complications of type 2 diabetes play an important role in decreasing life expectancy and adversely affecting quality of life. Diabetic nephropathy, which is originally microvascular in nature, is widely considered an important complication of diabetes. In prospective clinical investigations, increased urinary albumin excretion proved to be associated not only with subsequent renal outcomes but also with cardiovascular morbidity/mortality independently of other risk factors. Therefore, microalbuminuria as an early sign of increased urinary albumin excretion should be considered important for both treatment and even for prevention. Preventing microalbuminuria might diminish progression to overt nephropathy and, hopefully, might limit cardiovascular events. Regarding primary prevention of diabetic nephropathy, therapeutic intervention should optimally be initiated at the stage of normoalbuminuria. Although additional factors such as smoking cessation, reduction of protein intake, and treatment of lipid abnormalities are important, providing optimal diabetic control as well as targeting optimal blood pressure are the key elements of a prevention strategy in diabetic patients. Recently, the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) documented that a significant decrease of the development of persistent microalbuminuria could be achieved by using an ACE-inhibitor, trandolapril alone or in combination with verapamil SR, a non-dihydropyridine calcium-channel blocker in hypertensive type 2 diabetic patients with normoalbuminuria. The results of this primary-prevention strategy should be corroborated by further investigations to determine whether these beneficial changes could later result in improvement of renal clinical outcomes, macrovascular complications, or both.     

二甲双胍与利拉鲁肽对超重2型糖尿病患者肠道菌群的影响

目的 探究二甲双胍与利拉鲁肽对超重2型糖尿病患者肠道菌群结构和功能的影响.方法 选取2018年1月—2019年6月我院90例超重2型糖尿病患者作为研究对象,采用完全随机原则将其分为治疗方案不同的3组,分别为Met组(单用二甲双胍治疗)、Lira组(单用利拉鲁肽治疗)和Ct组(联合二甲双胍与利拉鲁肽治疗),采用高通量测序...     

The efficacy and tolerability of fosinopril in Chinese type 2 diabetic patients with moderate renal insufficiency

BACKGROUND: The renoprotective effect of angiotensin II antagonists has been demonstrated in type 2 diabetic patients with nephropathy but similar data on angiotensin-converting enzyme (ACE) inhibitors are limited. We examined the efficacy and tolerability of fosinopril, an ACE inhibitor with dual hepatic and renal clearance, in 38 type 2 diabetic patients with moderate renal impairment (plasma creatinine 130-300 micromol/l) over a 2-year period. METHODS: This was a single-centre, randomized, double-blinded, placebo-controlled trial comparing fosinopril 20 mg daily vs. placebo in addition to conventional antihypertensive treatment over a 2-year period. The primary endpoints were the rate of change and the percentage change in both 24-h urinary albumin excretion (UAE) and creatinine clearance (CrCl). RESULTS: The mean age of the patients was 65 +/- 6 years (range 47-76 years, median 66 years) and plasma creatinine 190 +/- 49 micromol/l. For similar blood pressure control, the percentage change of UAE in patients with microalbuminuria was greater in the fosinopril than the placebo group (-24.2 +/- 28.8 vs. 11.6 +/- 42.1%, p = 0.003 after adjustment for baseline covariates). In the fosinopril group, the rate of change of endogenous CrCl was slower than the placebo group (-0.07 +/- 0.19 vs. -0.24 +/- 0.35 ml/min/week, p = 0.026). The incidence of adverse events was similar between the two groups. CONCLUSIONS: Fosinopril treatment reduced albuminuria and rate of decline in renal function in type 2 diabetic patients with moderate renal insufficiency and did not increase the incidence of adverse events.     

Use of sodium-glucose co-transporter-2 inhibitors in Asian patients with type 2 diabetes and kidney disease: An Asian perspective and expert recommendations

Early onset of type 2 diabetes and a high prevalence of co-morbidities predispose the Asian population to a high risk for, and rapid progression of, diabetic kidney disease (DKD). Apart from renin-angiotensin system inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been shown to delay renal disease progression in patients with DKD. In this review article, we consolidate the existing literature on SGLT-2 inhibitor use in Asian patients with DKD to establish contemporary guidance for clinicians. We extensively reviewed recommendations from international and regional guidelines, data from studies on Asian patients with DKD, global trials (DAPA-CKD, CREDENCE and DELIGHT) and cardiovascular outcomes trials. In patients with DKD, SGLT-2 inhibitor therapy significantly reduced albuminuria and the risk of hard renal outcomes (defined as the onset of end-stage kidney disease, substantial decline in renal function from baseline and renal death), cardiovascular outcomes and hospitalization for heart failure. In all the cardiovascular and renal outcomes trials, there was an initial decline in the estimated glomerular filtration rate (eGFR), which was followed by a slowing in the decline of renal function compared with that seen with placebo. Despite an attenuation in glucose-lowering efficacy in patients with low eGFR, there were sustained reductions in body weight and blood pressure, and an increase in haematocrit. Based on the available evidence, we conclude that SGLT-2 inhibitors represent an evidence-based therapeutic option for delaying the progression of renal disease in Asian patients with DKD and preserving renal function in patients at high risk of kidney disease.