Type 2 diabetes is a progressive disease,1 and approximately 20% to 30% of individuals living with diabetes require some form of insulin treatment during their lifetime.2 The predominant reason for insulin requirement is a progressive loss of beta-cell function over time.

Basal insulin treatment followed by the addition of single/multiple prandial/bolus doses is frequently needed to achieve an adequate glycemic state and to sustain glycemic control. The joint European Association for the Study of Diabetes/American Diabetes Association recommends initiation of basal insulin based on the degree of hyperglycemia and body weight and recommends individualized titration as necessary to reach the HbA1c/glycemic target.3

Icodec is a novel basal insulin that has a very long half-life (approximately 196 hours), and a steady state is achieved after 3-4 weekly injections4 compared to the currently available basal insulins; hence, a once-weekly dose is proposed and has been used in clinical trials. However, before it is approved for marketing, it is imperative that newer basal insulins should be proven efficacious in terms of reducing HbA1c/fasting plasma glucose (FPG) and increasing time in range (TIR) (at least noninferior to the currently available once-daily basal insulins), should preferably reduce the incidence of hypoglycemia (especially nocturnal/severe hypoglycemia) and decrease parameters such as the time below range, should not increase the body weight inappropriately, and should ideally not require higher doses to achieve similar glycemic control (dose equivalence).

There are several open-label large and small randomized controlled trials (RCTs) (including phase 2 and phase 3a trials) of icodec of variable duration comparing it with either once-daily degludec or glargine-100 insulin.5, 6, 7, 8, 9, 10, 11 The populations included in these trials were either insulin naive or subjects who were already on some form of basal insulin with or without other oral glucose-lowering agents/injectable GLP-1 therapies. Although these trials have documented the effects of insulin icodec in individual study populations, we aimed to comprehensively evaluate its efficacy using all available literature from all RCTs that had variable diverse inclusion criteria and different background treatments.

Using the available studies comparing once-weekly icodec with once-daily glargine (the current gold standard) and degludec and based on the available information from these studies, either from the original article or supplementary data, we undertook this meta-analysis with the following research questions: Can lower mean HbA1c and fasting blood glucose (even though the studies were treat-to-target studies) be achieved? Is there any difference in the percentage of “time in range” achieved in the studies? Is there any difference in weight gain? Are there associated differences in overall hypoglycemia (especially severe hypoglycemia)?