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Incretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis

BMJ 2017; 357 doi: https://doi.org/10.1136/bmj.j2499 (Published 08 June 2017) Cite this as: BMJ 2017;357:j2499

Regulation of carbohydrate intake may be better than treatment of hyperglycaemia in patients with type 2 diabetes mellitus

Rajkumar Rajendram [1-3]
Ahmed Al Ibrahim [1]

1. Department of Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
2. Medication Use and Process Evaluation Subcommittee of the Medication Safety Program, Central Region, Ministry of National Guard Health Affairs, Saudi Arabia
3. Department of Nutrition and Dietetics, School of Biomedical and Life Sciences, King’s College London, UK

Mortality from diabetes is primarily due to cardiovascular disease.[1] However, before the United States Food and Drug Administration industry required data on cardiovascular outcomes (CVO) to license new hypoglycaemic agents in 2008; few studies had examined the relationship between glucose lowering drugs and cardiovascular (CV) risk. This paradigm shift encouraged the use of hypoglycaemic agents with mortality benefits.

It was therefore extremely disappointing that the meta-analysis of 189 studies of incretin-based treatment on all cause mortality in patients with type 2 diabetes reported by Liu et al.[2] found that there was no difference between incretin drugs and control. Indeed, Glucagon-like peptide-1 analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors have joined a long list of hypoglycaemic agents that do not improve cardiovascular outcomes or reduce mortality. This failure to identify hypoglycaemic medications that improve patient-relevant outcomes demands yet another paradigm shift in the management of type 2 diabetes.

Rather than attempting to control hyperglycaemia it may be more appropriate to prevent the development of hyperglycaemia. This may be achieved by regulation of carbohydrate intake. Cohort studies have suggested that whilst a carnivorous low-carbohydrate diet is associated with higher all-cause mortality; a vegetarian low-carbohydrate diet improves cardiovascular disease and reduces mortality.[3]

Although further research is required to confirm these data; such lifestyle modifications are extremely difficult to achieve and maintain.[4] Regardless, reducing morbidity and mortality from diabetes mellitus is critical to public health so a novel approach to the management is urgently required to improve outcomes.

REFERENCES

1. Khan SS, Butler J, Gheorghiade M. Management of comorbid diabetes mellitus and worsening heart failure. JAMA2014;311:2379-80.
2. Liu J, Li L, Deng K, Xu C, Busse JW, Vandvik PO, Li S, Guyatt GH, Sun X. Incretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis. BMJ. 2017;357:j2499.
3. Fung TT, van Dam RM, Hankinson SE, Stampfer M, Willett WC, Hu FB. Low-carbohydrate diets and all-cause and cause-specific mortality: two cohort studies. Ann Intern Med. 2010;153:289-98.
4. Norris SL, Engelgau MM, Venkat Narayan KM. Effectiveness of self-management training in type 2 diabetes: a systematic review of randomized controlled trials. Diabetes Care 2001;24:561--87.

Competing interests: No competing interests

12 August 2017
Rajkumar Rajendram
Consultant in Internal Medicine; Chairman of Medication Use and Process Evaluation Subcommittee of the Medication Safety Program
Ahmed Al Ibrahim
Department of Medicine
King Abdulaziz Medical City, Riyadh, Ministry of National Guard Health Affairs, Saudi Arabia
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