Reducing Type 1 Diabetes Mortality: Role for Adjunctive Therapies?

Snaith, Jennifer R; Holmes-Walker, D Jane; Greenfield, Jerry R.

doi:10.1016/j.tem.2019.11.007

Cited by 28 publications

(30 citation statements)

References 94 publications

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“…Metformin has been evaluated in numerous small trials in people with type 1 diabetes with hopes that its insulin-sensitising properties would improve glycaemic management and/or reduce cardiovascular risk [ 244 , 245 ]. The largest study to date assessed the use of metformin 1 g, twice daily, in 428 people with type 1 diabetes who were treated for 3 years, with a primary endpoint of changes in mean carotid intima–media thickness, a marker of cardiovascular disease risk.…”

Section: Section 13: Adjunctive Therapiesmentioning

confidence: 99%

“…In several Phase III programmes in people with type 1 diabetes, the use of SGLT-1 or SGLT-1/2 inhibitors reduced HbA 1c , improved TIR, reduced body weight and improved blood pressure [ 244 ]. However, an increased rate of DKA led to rejection of market authorisation for type 1 diabetes by the FDA, whereas the European Medicines Agency has approved low-dose dapagliflozin (5 mg) and sotagliflozin (200 mg) for those with a BMI ≥27 kg/m 2 [ 261 ].…”

Section: Section 13: Adjunctive Therapiesmentioning

confidence: 99%

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The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

et al. 2021

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The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a writing group to develop a consensus statement on the management of type 1 diabetes in adults. The writing group has considered the rapid development of new treatments and technologies and addressed the following topics: diagnosis, aims of management, schedule of care, diabetes self-management education and support, glucose monitoring, insulin therapy, hypoglycaemia, behavioural considerations, psychosocial care, diabetic ketoacidosis, pancreas and islet transplantation, adjunctive therapies, special populations, inpatient management and future perspectives. Although we discuss the schedule for follow-up examinations and testing, we have not included the evaluation and treatment of the chronic microvascular and macrovascular complications of diabetes as these are well-reviewed and discussed elsewhere. The writing group was aware of both national and international guidance on type 1 diabetes and did not seek to replicate this but rather aimed to highlight the major areas that healthcare professionals should consider when managing adults with type 1 diabetes. Though evidence-based where possible, the recommendations in the report represent the consensus opinion of the authors.

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Section: Section 13: Adjunctive Therapiesmentioning

confidence: 99%

Section: Section 13: Adjunctive Therapiesmentioning

confidence: 99%

The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

et al. 2021

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“…Yet metformin did not clearly prevent carotid ultrasound measures of atherosclerosis progression in a study of Type 1 adults 12 . Metformin enhances peripheral insulin sensitivity in Type 1 adolescents and improves some metabolic parameters (HbA1c, cholesterol, weight) 13,14 . Minor improvements in glycaemia, weight and lipids were also seen in a study of Type 1 adults treated with metformin for 3 years 12 .…”

Section: Introductionmentioning

confidence: 94%

Insulin resistance in type 1 diabetes managed with metformin (INTIMET): Study protocol of a double‐blind placebo‐controlled, randomised trial

et al. 2021

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Background Insulin resistance is an under‐recognised metabolic defect and cardiovascular risk factor in Type 1 diabetes. Whether metformin improves hepatic, muscle or adipose tissue insulin sensitivity has not been studied in adults with Type 1 diabetes. We initiated the INTIMET study (INsulin resistance in Type 1 diabetes managed with METformin), a double‐blind randomised, placebo‐controlled trial to measure the effect of metformin on tissue‐specific insulin resistance in adults with Type 1 diabetes. Methods We will study 40 adults aged 20–55 years with Type 1 diabetes (HbA1c ≤80 mmol/mol [9.5%], fasting C‐peptide <0.3 nmol/L) and 20 age‐, gender‐ and body mass index (BMI)‐matched controls. Insulin sensitivity will be determined by the two‐step hyperinsulinaemic‐euglycaemic clamp method with deuterated glucose to document liver, muscle and adipose insulin sensitivity. Subjects with Type 1 diabetes will be randomised to metformin extended‐release 1500 mg daily or matched placebo for 26 weeks. The primary outcome is change in hepatic insulin sensitivity, assessed by change in basal rate of appearance (Ra) of glucose and suppression of endogenous glucose production (EGP) during the low‐dose stage of the clamp. Conclusion The INTIMET study is the first clinical trial to quantify the impact of metformin on liver, muscle and adipose insulin resistance in adults with Type 1 diabetes. This study may identify factors that predict an individual's response to metformin in Type 1 diabetes. Trial Registration: ACTRN12619001440112.

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“…Non-insulin therapies, such as sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonist and dipeptidyl peptidase-4 inhibitors, have been investigated to try to improve glycemic control, as well as for their potential effect in CVD risk factors ( 65 ).…”

Section: Drug Interventions: Where Are We?mentioning

confidence: 99%

“…A large body of evidence support a positive effect of SGLT2-inhibitors on cardiovascular and renal outcomes in adults with diabetes, although data for the pediatric population are lacking ( 65 ). While these medications appear promising, the risk for euglycemic diabetic ketoacidosis is still a potential limiting factor to consider before a wide implementation in the pediatric population ( 65 ).…”

Section: Drug Interventions: Where Are We?mentioning

confidence: 99%

Preventing Cardiovascular Complications in Type 1 Diabetes: The Need for a Lifetime Approach

Chiesa

Marcovecchio

2021

Front. Pediatr.

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Cardiovascular disease (CVD) remains the main cause of morbidity and mortality in individuals with type 1 diabetes (T1D). Adolescence appears to be a critical time for the development of early subclinical manifestations of CVD, with these changes likely driven by a deterioration in glycemic control during the progression through puberty, combined with the emergence of numerous other traditional cardiometabolic risk factors (e.g., hypertension, dyslipidemia, smoking, alcohol use, obesity, etc.) which emerge at this age. Although hemoglobin A1C has long been the primary focus of screening and treatment strategies, glycemic control remains poor in youth with T1D. Furthermore, screening for cardiovascular risk factors—which are often elevated in youth with T1D—is suboptimal, and use of pharmacological interventions for hypertension and dyslipidemia remains low. As such, there is a clear need not only for better screening strategies for CVD risk factors in youth, but also early interventions to reduce these, if future CVD events have to be prevented. Accumulating evidence has recently suggested that early increases in urinary albumin excretion, even within the normal range, may identify adolescents with T1D who are at an increased risk of complications, and results from pharmacological intervention with statins and ACE inhibitors in these individuals have been encouraging. These data join a growing evidence highlighting the need for a whole-life approach to prevention starting from childhood if efforts to improve CVD outcomes and related mortality in T1D are to be maintained.

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Reducing Type 1 Diabetes Mortality: Role for Adjunctive Therapies?

Cited by 28 publications

References 94 publications

The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Insulin resistance in type 1 diabetes managed with metformin (INTIMET): Study protocol of a double‐blind placebo‐controlled, randomised trial

Preventing Cardiovascular Complications in Type 1 Diabetes: The Need for a Lifetime Approach

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