Automated insulin delivery/hybrid closed-loop insulin delivery
Automated insulin delivery/hybrid closed-loop insulin delivery uses an integrated system of a continuous glucose monitor, an insulin pump and a control algorithm that automatically modulates subcutaneous insulin delivery.[259]Sherr JL, Heinemann L, Fleming GA, et al. Automated insulin delivery: benefits, challenges, and recommendations. A Consensus Report of the Joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association. Diabetologia. 2023 Jan;66(1):3-22.
https://link.springer.com/article/10.1007/s00125-022-05744-z
http://www.ncbi.nlm.nih.gov/pubmed/36198829?tool=bestpractice.com
A small number of short-term studies have demonstrated the benefits of automated insulin delivery in adults with type 2 diabetes; however, its value in this population is not fully understood and requires further investigation.[259]Sherr JL, Heinemann L, Fleming GA, et al. Automated insulin delivery: benefits, challenges, and recommendations. A Consensus Report of the Joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association. Diabetologia. 2023 Jan;66(1):3-22.
https://link.springer.com/article/10.1007/s00125-022-05744-z
http://www.ncbi.nlm.nih.gov/pubmed/36198829?tool=bestpractice.com
In one open-label, single-centre, randomised crossover trial in adults with type 2 diabetes, automated insulin delivery improved glucose control without increasing hypoglycaemia compared with standard insulin therapy, with the authors concluding that this may represent a safe and efficacious method to improve patient outcomes.[260]Daly AB, Boughton CK, Nwokolo M, et al. Fully automated closed-loop insulin delivery in adults with type 2 diabetes: an open-label, single-center, randomized crossover trial. Nat Med. 2023 Jan;29(1):203-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9873557
http://www.ncbi.nlm.nih.gov/pubmed/36631592?tool=bestpractice.com
Automated insulin delivery systems have been studied more widely in patients with type 1 diabetes. The Association of British Clinical Diabetologists Closed-Loop Audit Program was designed to assess the real-world effectiveness and safety of hybrid closed-loop systems commercially available in the UK in an NHS outpatient setting for patients with type 1 diabetes with an HbA1c of ≥8.5%.[261]Crabtree TSJ, Griffin TP, Yap YW, et al. Hybrid closed-loop therapy in adults with type 1 diabetes and above-target HbA1c: a real-world observational study. Diabetes Care. 2023 Oct 1;46(10):1831-8.
https://diabetesjournals.org/care/article/46/10/1831/153467/Hybrid-Closed-Loop-Therapy-in-Adults-With-Type-1
http://www.ncbi.nlm.nih.gov/pubmed/37566697?tool=bestpractice.com
The study concluded that the use of hybrid closed-loop therapy is associated with improvements in HbA1c, time in range, hypoglycaemia, and diabetes-related distress and quality of life in people with type 1 diabetes.[261]Crabtree TSJ, Griffin TP, Yap YW, et al. Hybrid closed-loop therapy in adults with type 1 diabetes and above-target HbA1c: a real-world observational study. Diabetes Care. 2023 Oct 1;46(10):1831-8.
https://diabetesjournals.org/care/article/46/10/1831/153467/Hybrid-Closed-Loop-Therapy-in-Adults-With-Type-1
http://www.ncbi.nlm.nih.gov/pubmed/37566697?tool=bestpractice.com
Once-weekly insulin formulations
Basal insulin therapy may be needed in patients with type 2 diabetes, but there can be reluctance to initiate treatment due to the burden of the existing once-daily treatment regimens on the patient. A once-weekly insulin regimen may help to overcome this reluctance and improve overall treatment compliance. There are currently two once-weekly basal insulins in various stages of development: insulin icodec and basal insulin Fc (BIF; also known as insulin efsitora alfa). Insulin icodec is approved in Europe for the treatment of diabetes mellitus in adults. BIF is still under clinical development. The safety and efficacy of once-weekly insulin icodec has been assessed in patients with type 2 diabetes (both insulin-naive and previously insulin-treated insulin) in a series of phase 3a, randomised, clinical trials (the ONWARDS trials). Overall, the trials suggest that once-weekly insulin icodec shows non-inferior, and in some cases superior, glycaemic control compared with the once-daily insulin analogues insulin degludec and insulin glargine, with a similarly low rate of hypoglycaemia.[262]Philis-Tsimikas A, Asong M, Franek E, et al. Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial. Lancet Diabetes Endocrinol. 2023 Jun;11(6):414-25.
https://www.thelancet.com/journals/landia/article/PIIS2213-8587(23)00093-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/37148899?tool=bestpractice.com
[263]Mathieu C, Ásbjörnsdóttir B, Bajaj HS, et al. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial. Lancet. 2023 Jun 10;401(10392):1929-40.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00520-2/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/37156252?tool=bestpractice.com
[264]Lingvay I, Asong M, Desouza C, et al. Once-weekly insulin icodec vs once-daily insulin degludec in adults with insulin-naive type 2 diabetes: rhe ONWARDS 3 randomized clinical trial. JAMA. 2023 Jul 18;330(3):228-37.
https://jamanetwork.com/journals/jama/article-abstract/2806635
http://www.ncbi.nlm.nih.gov/pubmed/37354562?tool=bestpractice.com
[265]Rosenstock J, Bain SC, Gowda A, et al. Weekly Icodec versus daily glargine U100 in type 2 diabetes without previous insulin. N Engl J Med. 2023 Jul 27;389(4):297-308.
https://www.nejm.org/doi/10.1056/NEJMoa2303208?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://www.ncbi.nlm.nih.gov/pubmed/37356066?tool=bestpractice.com
[266]Bajaj HS, Aberle J, Davies M, et al. Once-weekly insulin icodec with dosing guide app versus once-daily basal insulin analogues in insulin-naive type 2 diabetes (ONWARDS 5): a randomized trial. Ann Intern Med. 2023 Sep 26.
https://www.acpjournals.org/doi/10.7326/M23-1288?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://www.ncbi.nlm.nih.gov/pubmed/37748181?tool=bestpractice.com
The safety and efficacy of once-weekly BIF versus once-daily degludec in insulin-naive patients with type 2 diabetes previously treated with oral antihyperglycaemic medications was assessed in a phase 2 randomised open-label study.[267]Bue-Valleskey JM, Kazda CM, Ma C, et al. Once-weekly basal insulin Fc demonstrated similar glycemic control to once-daily insulin degludec in insulin-naive patients with type 2 diabetes: a phase 2 randomized control trial. Diabetes Care. 2023 May 1;46(5):1060-7.
https://diabetesjournals.org/care/article/46/5/1060/148655/Once-Weekly-Basal-Insulin-Fc-Demonstrated-Similar
http://www.ncbi.nlm.nih.gov/pubmed/36944059?tool=bestpractice.com
It concluded that BIF achieved excellent glycaemic control similar to degludec, with no concerning hypoglycaemia or other safety findings.[267]Bue-Valleskey JM, Kazda CM, Ma C, et al. Once-weekly basal insulin Fc demonstrated similar glycemic control to once-daily insulin degludec in insulin-naive patients with type 2 diabetes: a phase 2 randomized control trial. Diabetes Care. 2023 May 1;46(5):1060-7.
https://diabetesjournals.org/care/article/46/5/1060/148655/Once-Weekly-Basal-Insulin-Fc-Demonstrated-Similar
http://www.ncbi.nlm.nih.gov/pubmed/36944059?tool=bestpractice.com
Bexagliflozin
The US Food and Drug Administration (FDA) has approved bexagliflozin, an oral sodium-glucose cotransporter-2 (SGLT2) inhibitor, as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes. Phase 3 clinical trials have studied bexagliflozin as monotherapy and in combination with metformin in adults with type 2 diabetes; it has also been studied in phase 3 trials in adults with type 2 diabetes and moderate renal impairment, and in adults with type 2 diabetes and established or increased risk of cardiovascular disease.[268]ClinicalTrials.gov. Safety and efficacy of bexagliflozin as monotherapy in patients with type 2 diabetes. June 2021 [internet publication].
https://clinicaltrials.gov/study/NCT02715258
[269]ClinicalTrials.gov. Safety and efficacy of bexagliflozin compared to placebo as add-on therapy to metformin in type 2 diabetes subjects. July 2021 [internet publication].
https://clinicaltrials.gov/study/NCT03259789
[270]ClinicalTrials.gov. Safety and efficacy of bexagliflozin compared to glimepiride as add-on therapy to metformin in type 2 diabetes subjects. May 2021 [internet publication].
https://clinicaltrials.gov/study/NCT02769481
[271]ClinicalTrials.gov. Safety and efficacy of bexagliflozin compared to sitagliptin as add-on therapy to metformin in type 2 diabetes subjects. June 2021 [internet publication].
https://clinicaltrials.gov/study/NCT03115112
[272]ClinicalTrials.gov. Safety and efficacy of bexagliflozin in type 2 diabetes mellitus patients with moderate renal impairment. June 2021 [internet publication].
https://clinicaltrials.gov/study/NCT02836873
[273]ClinicalTrials.gov. Bexagliflozin efficacy and safety trial (BEST). July 2021 [internet publication].
https://clinicaltrials.gov/study/NCT02558296
[274]Halvorsen YD, Lock JP, Zhou W, et al. A 24-week, randomized, double-blind, active-controlled clinical trial comparing bexagliflozin with sitagliptin as an adjunct to metformin for the treatment of type 2 diabetes in adults. Diabetes Obes Metab. 2019 Oct;21(10):2248-56.
https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.13801
http://www.ncbi.nlm.nih.gov/pubmed/31161692?tool=bestpractice.com
[275]Allegretti AS, Zhang W, Zhou W, et al. Safety and effectiveness of bexagliflozin in patients with type 2 diabetes mellitus and stage 3a/3b CKD. Am J Kidney Dis. 2019 Sep;74(3):328-37.
https://www.ajkd.org/article/S0272-6386(19)30665-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/31101403?tool=bestpractice.com
[276]Halvorsen YD, Conery AL, Lock JP, et al. Bexagliflozin as an adjunct to metformin for the treatment of type 2 diabetes in adults: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2023 Oct;25(10):2954-62.
https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.15192
http://www.ncbi.nlm.nih.gov/pubmed/37409573?tool=bestpractice.com
Treatment with bexagliflozin reduced HbA1c compared to placebo and efficacy was non-inferior to glimepiride and sitagliptin, with reduction in HbA1c being shown across subgroups of age, sex, race, and geographic region. Bexagliflozin is not available in Europe.
Sotagliflozin
Sotagliflozin is the first dual SGLT1/SGLT2 inhibitor.[277]Cefalo CMA, Cinti F, Moffa S, et al. Sotagliflozin, the first dual SGLT inhibitor: current outlook and perspectives. Cardiovasc Diabetol. 2019 Feb 28;18(1):20.
https://cardiab.biomedcentral.com/articles/10.1186/s12933-019-0828-y
http://www.ncbi.nlm.nih.gov/pubmed/30819210?tool=bestpractice.com
It inhibits both renal SGLT-2 (promoting significant excretion of glucose in the urine, in the same way as other already available SGLT-2 selective inhibitors) and intestinal SGLT-1 (delaying glucose absorption and therefore reducing postprandial glucose).[277]Cefalo CMA, Cinti F, Moffa S, et al. Sotagliflozin, the first dual SGLT inhibitor: current outlook and perspectives. Cardiovasc Diabetol. 2019 Feb 28;18(1):20.
https://cardiab.biomedcentral.com/articles/10.1186/s12933-019-0828-y
http://www.ncbi.nlm.nih.gov/pubmed/30819210?tool=bestpractice.com
It is available as an oral formulation. It has been approved by the FDA to reduce the risk of cardiovascular death, hospitalisation for heart failure, and urgent heart failure visits in adults with heart failure, or with type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors. The approval was based on two randomised, double-blind, placebo-controlled phase 3 cardiovascular outcome trials: SOLOIST-WHF (effects of sotagliflozin on clinical outcomes in haemodynamically stable patients with type 2 diabetes post worsening heart failure) and SCORED (effects of sotagliflozin on cardiovascular and renal events in patients with type 2 diabetes mellitus, cardiovascular risk factors and moderately impaired renal function).[278]Bhatt DL, Szarek M, Pitt B, et al. Sotagliflozin in patients with diabetes and chronic kidney disease. N Engl J Med. 2021a Jan 14;384(2):129-39.
https://www.nejm.org/doi/10.1056/NEJMoa2030186?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://www.ncbi.nlm.nih.gov/pubmed/33200891?tool=bestpractice.com
[279]Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. 2021b Jan 14;384(2):117-28.
https://www.nejm.org/doi/10.1056/NEJMoa2030183?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://www.ncbi.nlm.nih.gov/pubmed/33200892?tool=bestpractice.com
Sotagliflozin is not available in Europe.
Bempedoic acid
Bempedoic acid, an adenosine triphosphate-citrate lyase inhibitor, is a novel oral low-density lipoprotein cholesterol-lowering drug. It is approved in Europe for the treatment of adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet either in combination with a statin (or a statin with other lipid-lowering therapies) in patients unable to reach LDL cholesterol goals with the maximum tolerated dose of a statin, or alone/in combination with other lipid-lowering therapies in patients who are statin-intolerant or for whom a statin is contraindicated. Bempedoic acid is also approved for a similar indication in the US and is recommended by the American Diabetes Association for people with diabetes intolerant to statin therapy.[34]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care. 2024 Jan;47(suppl 1):S1-321.
https://diabetesjournals.org/care/issue/47/Supplement_1
A NICE technology appraisal recommends using bempedoic acid with ezetimibe as an option for treating primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia as an adjunct to diet in adults if statins are contraindicated or not tolerated, ezetimibe alone does not control LDL cholesterol well enough, and the company provides bempedoic acid and bempedoic acid with ezetimibe according to the commercial arrangement.[280]National Institute for Health and Care Excellence. Bempedoic acid with ezetimibe for treating primary hypercholesterolaemia or mixed dyslipidaemia. April 2021 [internet publication].
https://www.nice.org.uk/guidance/ta694
There is emerging evidence from one RCT that treatment with bempedoic acid is associated with a reduction in risk of major adverse cardiovascular events (death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularisation) in statin-intolerant patients, providing some evidence for its use in this group.[281]Nissen SE, Lincoff AM, Brennan D, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med. 2023 Apr 13;388(15):1353-64.
https://www.nejm.org/doi/10.1056/NEJMoa2215024?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://www.ncbi.nlm.nih.gov/pubmed/36876740?tool=bestpractice.com
Endoscopic bariatric procedures
Stand-alone, primary endoscopic bariatric procedures (e.g., intragastric balloons) for the management of obesity and certain obesity-associated comorbidities like type 2 diabetes have evolved in recent years, bridging the gap between intensive lifestyle modifications and invasive bariatric surgical procedures.[28]World Gastroenterology Organisation and International Federation for the Surgery of Obesity and Metabolic Diseases. IFSO-WGO guidelines on obesity. 2023 [internet publication].
https://www.worldgastroenterology.org/guidelines/obesity/obesity-english
In general, endoscopic bariatric procedures appear to be slightly less efficacious than bariatric surgery, although they are potentially slightly safer, less-invasive, and more reversible.[28]World Gastroenterology Organisation and International Federation for the Surgery of Obesity and Metabolic Diseases. IFSO-WGO guidelines on obesity. 2023 [internet publication].
https://www.worldgastroenterology.org/guidelines/obesity/obesity-english