Treatment of patients with type 2 diabetes with exenatide once weekly versus oral glucose-lowering medications or insulin glargine: achievement of glycemic and cardiovascular goals

Abstract Objective To examine diabetes remission following a short-term intensive metabolic intervention combining lifestyle and glucose-lowering approaches. Methods We conducted an open-label, randomized controlled trial in 154 patients with type 2 diabetes up to 8 years in duration on 0 to 2 glucose-lowering medications. Participants were randomized to (a) a 12-week intensive intervention comprising lifestyle approaches and treatment with insulin glargine, metformin, and dapagliflozin or (b) standard diabetes care. At 12 weeks, diabetes medications were discontinued in participants with hemoglobin A1c (HbA1C) < 7.3% (56 mmol/mol). Participants were then followed for diabetes relapse until 64 weeks. The primary outcome was complete or partial diabetes remission (HbA1C < 6.5% [48 mmol/mol] off chronic diabetes drugs) at 24 weeks. Main secondary outcomes were complete or partial diabetes remission at 36, 48, and 64 weeks. Results The primary outcome was achieved in 19 (24.7%) intervention group participants and 13 (16.9%) control group participants at 24 weeks (relative risk [RR] 1.5; 95% confidence interval [CI], 0.8-2.7). The relative risks of remission at 36, 48, and 64 weeks were 2.4 (95% CI, 1.2-5.0), 2.1 (95% CI, 1.0-4.4), and 1.8 (95% CI, 0.7-4.7), respectively. In an exploratory analysis, the intervention reduced the hazard of diabetes relapse with overt hyperglycemia by 43% (hazard ratio 0.57; 95% CI, 0.39-0.81). Conclusions Our primary outcome of diabetes remission at 24 weeks was not statistically significantly different. However, our overall results suggest that some patients with early type 2 diabetes are able to achieve sustained diabetes remission following a short-term intensive intervention. Further studies are needed to optimize the combined therapeutic approach used.

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P1028EFFECTS OF CANAGLIFLOZIN ON MAJOR ADVERSE CARDIOVASCULAR OUTCOMES IN PATIENTS WITH DIFFERENT BASELINE LEVELS OF TYPE 2 DIABETES MELLITUS DISEASE SEVERITY: RESULTS FROM THE CANVAS PROGRAM

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1028 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Tamara Young ◽

Jing-wei Li ◽

Amy Kang ◽

Hiddo Heerspink ◽

Carinna Hockham ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Disease Severity ◽

Cardiovascular Outcomes ◽

Oral Glucose ◽

Glucose Lowering ◽

Duration Of Diabetes ◽

Event Rates

Abstract Background and Aims Patient with type 2 diabetes mellitus (T2DM) included in trials of sodium-glucose cotransporter 2 inhibitors are heterogeneous in terms of disease severity. We assessed the effects of canagliflozin compared to placebo on cardiovascular and renal outcomes in the CANVAS program according to severity of T2DM as indicated by intensity of treatment, duration of diabetes and glycaemic control. Method We compared effects on major adverse cardiovascular events ([MACE], defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) according to three indicators of T2DM severity at study baseline: number of oral glucose lowering treatments or insulin therapy (0-1, 2, 3+, insulin), duration of diabetes (<10, 10-16, >16 years) and HbA1c (<7.0, 7.0-7.5, 7.5-8.0, 8.0-8.5, 8.5-9, >9.0%). We also assessed effects on other pre-specified cardiovascular outcomes, and an adjudicated composite of end-stage kidney disease, renal death or sustained 40% decline in estimated glomerular filtration rate. We assessed for constancy of hazard ratios across subgroups by fitting an interaction term that tested for linear trend. Results Of 10,142 participants in the CANVAS Program, 1011 experienced a MACE during a mean follow-up of 3.6 years. Event rates for MACE were higher in those with longer duration of diabetes and higher HbA1c at baseline. The effect of canagliflozin on MACE in the overall population (HR 0.86, 95 % CI 0.75-0.97) was consistent irrespective of the number of glucose lowering treatments (p=0.509), duration of diabetes (p=0.174) and baseline HbA1c (p =0.314). Effects were also consistent across different levels of T2DM disease severity for all other outcomes studied. Conclusion Higher event rates were observed in those with longer disease duration and higher HbA1c. The proportional risk reductions achieved with canagliflozin were comparable regardless of diabetes duration, number of therapies or HbA1C at baseline.

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