Title: Tirzepatide for treating type 2 diabetes [ID3938]
Funder: Department of Health and Social Care

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)[1] . If not managed effectively, diabetes mellitus can lead to kidney failure, blindness, foot problems, and damage to the nervous system[2] . People with diabetes are also more at risk of cardiovascular disease[3] . _x000D_ _x000D_ There were 3.3 million people in England with diagnosed diabetes mellitus in 2019, of which around 90% had type 2 diabetes[4] . However, an estimated 1 million further people have undiagnosed type 2 diabetes in the UK[4] . The UK prevalence of type 2 diabetes is rising, which has been linked to an increasing prevalence of obesity[5] . People from Black African, African Caribbean and South Asian family backgrounds are at a higher risk of developing type 2 diabetes from a younger age[6] . _x000D_ _x000D_ 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 blood glucose levels are not controlled by diet and exercise alone: _x000D_ _x000D_ • NICE guideline 28 recommends first-line drug treatment with standard release metformin. For people with chronic heart failure, cardiovascular disease or at high risk of cardiovascular disease, it recommends considering a selective sodium glucose-cotransporter 2 (SGLT2) inhibitor in addition to metformin. _x000D_ _x000D_ • When metformin is contraindicated or not tolerated a dipeptidyl peptidase-4 (DPP-4) inhibitor, pioglitazone or a sulfonylurea is recommended. For people with chronic heart failure, cardiovascular disease or at high risk of cardiovascular disease, or for people who meet the criteria in NICE technology appraisal guidance 390, or TA572, an SGLT2 inhibitor is recommended. _x000D_ _x000D_ When there is inadequate glycaemic control following first-line treatment, treatment is intensified: _x000D_ _x000D_ • NICE guideline 28 recommends adding a DPP-4 inhibitor, pioglitazone or a sulfonylurea, or an SGLT2 inhibitor for people who meet the criteria in NICE technology appraisal guidance 315, TA572, TA288, or TA336. _x000D_ If there is inadequate glycaemic control with dual therapy, treatment is intensified further:_x000D_ _x000D_ • NICE guideline 28 recommends triple therapy by adding a DPP-4 inhibitor, pioglitazone or a sulfonylurea, or an SGLT2 inhibitor for people who meet the criteria in NICE technology appraisal guidance 315, TA418, TA336, or TA583, or starting insulin-based treatment. _x000D_ _x000D_ • If metformin is contraindicated or not tolerated, NICE guideline 28 recommends insulin-based treatment. _x000D_ _x000D_ • If triple therapy with metformin and 2 other oral drugs is not effective, not tolerated or contraindicated, NICE guideline 28 recommends switching one drug for a glucagon-like peptide-1 (GLP-1) mimetic for some groups of people._x000D_ _x000D_ References_x000D_ 1. NHS Diabetes. Accessed January 2022_x000D_ 2. Diabetes UK Complications of diabetes. Accessed January 2022_x000D_ 3. Diabetes UK Diabetes and heart disease. Accessed January 2022_x000D_ 4. Diabetes UK Diabetes prevalence 2019. Accessed January 2022_x000D_ 5. Diabetes.co.uk Diabetes prevalence. Accessed January 2022_x000D_ 6. Diabetes UK Ethnicity and type 2 diabetes. Accessed January 2022

Lay abstract: To appraise the clinical and cost effectiveness of tirzepatide within its marketing authorisation for treating type 2 diabetes.

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