Title: Ertugliflozin (combination therapy with metformin) for treating type 2 diabetes [ID1160]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of ertugliflozin within its marketing authorisation for treating type 2 diabetes.

Lay abstract: Diabetes mellitus is a chronic metabolic disorder characterised by elevated blood glucose levels (hyperglycaemia) resulting from a lack of the hormone insulin or resistance to its action. Type 2 diabetes results from reduced insulin secretion or reduced tissue sensitivity to insulin (known as insulin resistance). If not managed effectively, diabetes mellitus can lead to kidney failure, blindness, limb amputation, and damage to the nervous system, peripheral vasculature and skin. Cardiovascular disease is the most common complication of type 2 diabetes and is the greatest cause of morbidity and premature death. Life expectancy is reduced by up to 10 years in people with diabetes. There were over 3 million people aged 17 and over in England with diagnosed diabetes mellitus in 2017.(1) However, many people with type 2 diabetes are undiagnosed, and so the number of people with the condition may be higher than reported. The UK prevalence of type 2 diabetes is rising because of increased prevalence of obesity, decreased physical activity and increased life expectancy after diagnosis because of better cardiovascular risk protection. Type 2 diabetes is particularly prevalent in people of African, South Asian and Caribbean family origin. NICE guideline 28 ‘type 2 diabetes in adults: management’ recommends reinforcing advice on diet, lifestyle and adherence to drug treatment for all people with type 2 diabetes. If there is inadequate glycaemic control on diet and exercise alone: ? NG28 recommends standard release metformin. When metformin is contraindicated or not tolerated a dipeptidyl peptidase-4 (DPP-4) inhibitor, pioglitazone or a sulfonylurea is recommended. ? NICE technology appraisal 390 recommends the selective sodium glucose-cotransporter 2 (SGLT-2) inhibitors canagliflozin, dapagliflozin and empagliflozin as options for monotherapy in adults for whom metformin is contraindicated or not tolerated and when diet and exercise alone do not provide adequate glycaemic control, only if a DPP-4 inhibitor would otherwise be prescribed and a sulfonylurea or pioglitazone is not appropriate. When there is inadequate glycaemic control following initial therapy, treatment is intensified: ? NICE guideline 28 recommends dual therapy with metformin plus a DPP-4 inhibitor, pioglitazone or a sulfonylurea. When metformin is contraindicated or not tolerated alternative dual therapies such as a DPP-4 inhibitor and pioglitazone, a DPP-4 inhibitor and a sulfonylurea or pioglitazone and a sulfonylurea are recommended. ? NICE technology appraisals 315, 288 and 336 recommend a SGLT-2 inhibitor (canagliflozin, dapagliflozin and empagliflozin respectively) in a dual therapy regimen with metformin, only if a sulfonylurea is contraindicated or not tolerated or the person is at significant risk of hypoglycaemia or its consequences. If there is inadequate glycaemic control following first intensification, treatment is intensified further: ? NICE guideline 28 recommends triple therapy with metformin (this includes metformin plus a sulfonylurea plus either a DPP-4 inhibitor or pioglitazone) or insulin based treatment. A glucagon-like peptide-1 (GLP-1) mimetic can be combined with metformin and sulfonylurea for specific subgroups if triple therapy is not effective, not tolerated or is contraindicated. ? NICE technology appraisal 418 recommends that triple therapy with dapagliflozin is a treatment option only in combination with metformin and a sulfonylurea. NICE technology appraisals 315 and 336 recommend that triple therapy with canagliflozin or empagliflozin are options in combination with either metformin plus a sulfonylurea or metformin plus a thiazolidinedione (pioglitazone). Canagliflozin, dapagliflozin and empagliflozin are also recommended as treatment options with insulin with or without other antidiabetic drugs. References 1. Quality and outcomes framework (QOF) for 2016-17 (2017). Accessed May 2018.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: METABOLIC AND ENDOCRINE