Effect of Patients’ Risks and Preferences on Health Gains With Plasma Glucose Level Lowering in Type 2 Diabetes Mellitus

Vijan, Sandeep; Sussman, Jeremy B.; Yudkin, John; Hayward, Rodney A.

doi:10.1001/jamainternmed.2014.2894

Cited by 163 publications

(135 citation statements)

References 63 publications

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“…Vijan et al 74 used data from the UKPDS to model probable benefits of improving glycaemic control at different ages and by different means (metformin, insulin), taking into account the burden of treatment. For older people the benefits of intensifying treatment could be outweighed by even minor AEs and other inconvenience.…”

Section: Targetsmentioning

confidence: 99%

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

Johnston

Uthman

Cummins

et al. 2017

Health Technol Assess

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Background Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium–glucose co-transporter 2 (SGLT2) inhibitors. Objective To review the clinical effectiveness and cost-effectiveness of dapagliflozin (Farxiga, Bristol-Myers Squibb, Luton, UK), canagliflozin (Invokana, Janssen, High Wycombe, UK) and empagliflozin (Jardiance, Boehringer Ingelheim, Ingelheim, Germany/Eli Lilly and Company, Indianapolis, IN, USA), in monotherapy in people who cannot take metformin. Sources MEDLINE (1946 to February 2015) and EMBASE (1974 to February 2015) for randomised controlled trials lasting 24 weeks or more. For adverse events, a wider range of studies was used. Three manufacturers provided submissions. Methods Systematic review and economic evaluation. A network meta-analysis was carried out involving the three SGLT2 inhibitors and key comparators. Critical appraisal of submissions from three manufacturers. Results We included three trials of dapagliflozin and two each for canagliflozin and empagliflozin. The trials were of good quality. The canagliflozin and dapagliflozin trials compared them with placebo, but the two empagliflozin trials included active comparators. All three drugs were shown to be effective in improving glycaemic control, promoting weight loss and lowering blood pressure (BP). Limitations There were no head-to-head trials of the different flozins, and no long-term data on cardiovascular outcomes in this group of patients. Most trials were against placebo. The trials were done in patient groups that were not always comparable, for example in baseline glycated haemoglobin or body mass index. Data on elderly patients were lacking. Conclusions Dapagliflozin, canagliflozin and empagliflozin are effective in improving glycaemic control, with added benefits of some reductions in BP and weight. Adverse effects are urinary and genital tract infections in a small proportion of users. In monotherapy, the three drugs do not appear cost-effective compared with gliclazide or pioglitazone, but may be competitive against sitagliptin (Januvia, Merck Sharp & Dohme Limited, Kenilworth, NJ, USA). Funding The National Institute for Health Research Health Technology Assessment programme.

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Section: Targetsmentioning

confidence: 99%

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

Johnston

Uthman

Cummins

et al. 2017

Health Technol Assess

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“…Previous modelling simulation studies have reported outcomes on one or two targeted HbA 1c reductions or for microvascular outcomes only [8][9][10]. To our knowledge, this is the first study to report on multiple HbA 1c targets for both micro-and macrovascular complications.…”

Section: Discussionmentioning

confidence: 92%

Modelling incremental benefits on complications rates when targeting lower HbA_1c levels in people with Type 2 diabetes and cardiovascular disease

et al. 2017

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Aim Glucose-lowering interventions in Type 2 diabetes mellitus have demonstrated reductions in microvascular complications and modest reductions in macrovascular complications. However, the degree to which targeting different HbA 1c reductions might reduce risk is unclear.Methods Participant-level data for Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) participants with established cardiovascular disease were used in a Type 2 diabetes-specific simulation model to quantify the likely impact of different HbA 1c decrements on complication rates. Ten-year micro-and macrovascular rates were estimated with HbA 1c levels fixed at 86, 75, 64, 53 and 42 mmol/mol (10%, 9%, 8%, 7% and 6%) while holding other risk factors constant at their baseline levels. Cumulative relative risk reductions for each outcome were derived for each HbA 1c decrement.Results Of 5717 participants studied, 72.0% were men and 74.2% White European, with a mean (SD) age of 66.2 (7.9) years, systolic blood pressure 134 (16.9) mmHg, LDL-cholesterol 2.3 (0.9) mmol/l, HDL-cholesterol 1.13 (0.3) mmol/l and median Type 2 diabetes duration 9.6 (5.1-15.6) years. Ten-year cumulative relative risk reductions for modelled HbA 1c values of 75, 64, 53 and 42 mmol/mol, relative to 86 mmol/mol, were 4.6%, 9.3%, 15.1% and 20.2% for myocardial infarction; 6.0%, 12.8%, 19.6% and 25.8% for stroke; 14.4%, 26.6%, 37.1% and 46.4% for diabetesrelated ulcer; 21.5%, 39.0%, 52.3% and 63.1% for amputation; and 13.6%, 25.4%, 36.0% and 44.7 for single-eye blindness.Conclusions These simulated complication rates might help inform the degree to which complications might be reduced by targeting particular HbA 1c reductions in Type 2 diabetes.

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“…In summary, although there are no absolute contraindications to use of any of the oral or injectable agents available for treating diabetes, there are special considerations for prescribing and monitoring of these agents in older adults that can impact cardiovascular safety, including risk for hypoglycemia and patient preference (10,20).…”

Section: Treatment Strategies For Achieving Glycemic Goals In Older Amentioning

confidence: 99%

“…These indirect analytic methods are problematic in that older adults with diabetes tend to be more heterogeneous and clinically complex than the younger populations (1,7,19). While most trials focus on mortality end points, many seniors may be more concerned with HRQL, functional capacity, and independence (20).…”

mentioning

confidence: 99%

Management of Atherosclerotic Cardiovascular Disease Risk Factors in the Older Adult Patient With Diabetes

Korytkowski

Forman

2017

Diabetes Care

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Older adults with diabetes are at higher risk for atherosclerotic cardiovascular disease (ASCVD) than younger adults with diabetes and older adults without diabetes. The rationale to implement ASCVD risk-lowering therapies in older adults with diabetes is compelling. Recommendations for lifestyle modification, lipidlowering therapy, blood pressure management, blood glucose control, and aspirin therapy are often based on studies that show their efficacy in younger populations. However, the risks associated with each of these interventions increase with age, and favorable risk-to-benefit ratios demonstrated in younger adults with diabetes are less certain in older populations. The variability in health status among older adults is pertinent. Those with robust health are more likely to tolerate and derive benefit from many therapies when compared with those who have more complex health including frailty. Age-and/or frailty-stratified data to help clarify these relationships are sparse. In this Perspective, current recommendations for modifying ASCVD risk are described with a review of the pertinent literature that guides their application in older adults. A pragmatic approach to the treatment of ASCVD risk factors in older adults with diabetes is presented.Diabetes is highly prevalent in the aging population, affecting .25% of individuals aged .65 years and 19% of those aged .75 years (1,2). Physiological changes associated with aging increase susceptibility to coronary heart disease and other atherosclerotic cardiovascular disease (ASCVD) processes (3). The incidence and prevalence of ASCVD-related macrovascular events essentially doubles in older adults with diabetes (4-6). The overlap of older age, diabetes, and other ASCVD risk factors enhances risk for microvascular and macrovascular complications, functional disability, and geriatric syndromes (including frailty, multimorbidity, polypharmacy, cognitive impairment, depression, urinary incontinence, and falls) (1,7-10). As the population of older adults grows, the implications of diabetes on ASCVD risk escalate, and insights regarding optimal care become increasingly important (2).Therapies directed at ASCVD risk factor reduction are important therapeutic priorities for older adults with diabetes as a way of modifying risk for vascular events and improving health-related quality of life (HRQL) (11,12). Therapeutic targets include control of lipids, blood pressure (BP), and blood glucose in combination with antiplatelet agents. The expectation is that these therapies will increase longevity, reduce ASCVD events and need for hospitalizations, and improve HRQL. However, iatrogenic risks and limited life expectancy confound these objectives

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Effect of Patients’ Risks and Preferences on Health Gains With Plasma Glucose Level Lowering in Type 2 Diabetes Mellitus

Cited by 163 publications

References 63 publications

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

Modelling incremental benefits on complications rates when targeting lower HbA_1c levels in people with Type 2 diabetes and cardiovascular disease

Management of Atherosclerotic Cardiovascular Disease Risk Factors in the Older Adult Patient With Diabetes

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Effect of Patients’ Risks and Preferences on Health Gains With Plasma Glucose Level Lowering in Type 2 Diabetes Mellitus

Cited by 163 publications

References 63 publications

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

Modelling incremental benefits on complications rates when targeting lower HbA1c levels in people with Type 2 diabetes and cardiovascular disease

Management of Atherosclerotic Cardiovascular Disease Risk Factors in the Older Adult Patient With Diabetes

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Modelling incremental benefits on complications rates when targeting lower HbA_1c levels in people with Type 2 diabetes and cardiovascular disease