Bile Acid Sequestrants as a Therapeutic Option for Glucose Lowering in Type 2 Diabetes Mellitus

2008 ◽  
Vol 14 (5) ◽  
pp. 644-647 ◽  
Author(s):  
Philip Levy
Author(s):  
Najla Shamsi

Type 2 Diabetes Mellitus is a prevalent chronic disease with several macrovascular and microvascular complications. Cardiovascular diseases including coronary artery disease and stroke are common macrovascular complication that reduces the quality of life and lead to early mortality. Additionally, they pose enormous socioeconomic burden on the societies and the governments. Therefore, any intervention that reduces the cardiovascular events in patients with diabetes will have positive impact of the patients and the society. Thus, this systematic review aimed to evaluate the cardiovascular events after metabolic surgery in comparison with the new classes of glucose lowering agents in patients with type 2 diabetes mellitus. The review included 11 randomized controlled trials to both GLP-1 RA and SGLT-2 i groups. It also included 7 metabolic surgery studies, 2 of these are randomized controlled trials and the other 5 are observational studies. These studies were the most relevant studies to the research question. The results revealed different baseline demographic and clinical characteristics between the medication trials and metabolic surgery studies. Moreover, it revealed significant reduction in cardiovascular events in metabolic surgery studies when compared to medication trials. It also showed significant HbA1c and weight reduction in the metabolic surgery group. The remission of diabetes was very high in the metabolic surgery group while none of medication trials accomplished diabetes recovery. However, both medication and surgery groups had adverse events. In conclusion, the review is consistent with previous literature. It suggests that metabolic surgery is more effective than medical therapy in reducing cardiovascular events. Although this conclusion should be interpreted with caution due to the differences in baseline characteristics between studies. In general, the review recommends younger adult diabetic patients with obesity and history of established cardiovascular diseases to undergo metabolic surgery. Whereas, older patients with history of cardiovascular disease should be advised to take one of the medications that has been proved to reduce cardiovascular events. Future studies that compare metabolic surgery and the new classes of the glucose lowering agents is recommended to confirm the findings in this review.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Tamara Young ◽  
Jing-wei Li ◽  
Amy Kang ◽  
Hiddo Heerspink ◽  
Carinna Hockham ◽  
...  

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.


2017 ◽  
Vol 125 (07) ◽  
pp. 419-435 ◽  
Author(s):  
Lawrence Leiter ◽  
Michael Nauck

AbstractFor patients with type 2 diabetes mellitus, glucagon-like peptide-1 receptor agonists (GLP-1RAs) generally exert robust glucose-lowering effects that are at least as effective as insulin. As monotherapies, changes from baseline in HbA1c with GLP-1RAs ranged from –1.9 to –0.7% in phase 3 trials. In addition, GLP-1RAs confer a low risk of hypoglycaemia and have a body-weight advantage (changes from baseline ranging from –4.0 to –0.4 kg). There is also evidence of significant reductions in risk for cardiovascular events with some of these agents, with a number of other trials underway. Gastrointestinal adverse events typically increase with GLP-1RAs, although these are generally mild to moderate in intensity and rarely require treatment discontinuation. The GLP-1RAs that are commercially available or in development vary in structure and pharmacokinetics. These differences affect the frequency of administration and can also affect their relative efficacy and safety. This review summarizes the findings of phase 3 glycaemic control trials of available GLP-1RAs and considers them in the context of the distinct clinical needs of individual patients.


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