Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials

Abstract

Objective To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options. Design Systematic review and network meta-analysis. Data sources Ovid Medline, Embase, and Cochrane Central up to 14 October 2022. Eligibility criteria for selecting studies Eligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach. Results The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference −8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes ( https://matchit.magicevidence.org/230125dist-diabetes ). Conclusions This network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes. Systematic review registration PROSPERO CRD42022325948.

Favorable outcomes in Hispanic recipients receiving simultaneous pancreas kidney transplantation

“…Patients with diabetes and high BMI may benefit from weight loss reduction and medical management with glucagon‐like peptide 1 (GLP‐1) agonists. Therefore, future research should explore the outcomes of patients with diabetes treated with GLP‐1 agonists and sodium‐glucose co‐transporter 2 inhibitors, which provide metabolic and cardiovascular benefits, and compare them to the metabolic benefits of a pancreas transplant 51–54 …”

What is new in diabetes care and self-management?

“…4.5 The effect on weight should be considered when choosing glucose-lowering and other medications. 1,3 In addition, referral to a registered dietitian nutritionist for Medical Nutrition Therapy should be made at diagnosis and annually. 1,4,5 Although weight management has always been part of diabetes care, the 2023 Standards support higher levels of weight loss of up to 10% to 15% of body weight to improve glucose outcomes and decrease risks for heart disease.…”

“…Because the action of both DPP-4 and GLP-1 medications are glucose-dependent, the risk of hypoglycemia when taking these medications is low. 3,[6][7][8] Adverse reactions include unintentional weight loss and gastrointestinal problems, such as nausea, gastric pain, and www.Nursing2023.com November l Nursing2023 l 11 flulike symptoms. Dual incretin medications, such as tirzepatide, are newer and include both GIP and GLP-1 agonists.…”

“…The expanded use of sodiumglucose cotransporter-2 (SGLT2) inhibitors to reduce the development and progression of heart failure in those with type 2 diabetes was also incorporated. 1,3 SGLT-2 inhibitors are more effective than other medications in reducing end-stage kidney disease. 3 The threshold for initiation of an SGLT-2 inhibitor medication is now recommended at an estimated glomerular filtration rate (eGFR) of 20 mL/min per 1.73 m 2 or greater and urinary albumin of 200 mg/g creatinine or more.…”

“…1,3 SGLT-2 inhibitors are more effective than other medications in reducing end-stage kidney disease. 3 The threshold for initiation of an SGLT-2 inhibitor medication is now recommended at an estimated glomerular filtration rate (eGFR) of 20 mL/min per 1.73 m 2 or greater and urinary albumin of 200 mg/g creatinine or more. 1 A referral to nephrology is also recommended with increasing albumin or decreasing eGFR levels or a measured eGFR of 30 mL/min per 1.73 m 2 .…”