Safety and efficacy of insulin degludec/liraglutide (IDegLira) added to sulphonylurea alone or to sulphonylurea and metformin in insulin‐naïve people with Type 2 diabetes: the DUAL IV trial

Abstract

AimTo investigate the safety and efficacy of insulin degludec/liraglutide (IDegLira), a novel combination product, as add‐on therapy for people with Type 2 diabetes uncontrolled on sulphonylurea therapy.MethodsIn this 26‐week, double‐blind trial, adults with Type 2 diabetes [HbA1c 53–75 mmol/mol (7.0–9.0%)] were randomized to IDegLira (n = 289) or placebo (n = 146) as add‐on to pre‐trial sulphonylurea ± metformin, titrating to a fasting glycaemic target of 4.0–6.0 mmol/l. Treatment initiation was at 10 dose steps, and maximum dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide).ResultsThe mean HbA1c decreased from 63 mmol/mol (7.9%) to 46 mmol/mol (6.4%) with IDegLira and to 57 mmol/mol (7.4%) with placebo [estimated treatment difference –11 mmol/mol (95% CI –13; –10) or –1.02% (95% CI –1.18; –0.87); P < 0.001]. The HbA1c target of 53 mmol/mol (<7%) was achieved by 79.2% of participants in the IDegLira group vs 28.8% in the placebo group [estimated odds ratio 11.95 (95% CI 7.22; 19.77); P < 0.001]. Mean weight change was +0.5 kg with IDegLira vs –1.0 kg with placebo [estimated treatment difference 1.48 kg (95% CI 0.90; 2.06); P < 0.001]. Confirmed hypoglycaemia occurred in 41.7 and 17.1% of IDegLira‐ and placebo‐treated participants, respectively, with rates of 3.5 vs 1.4 events/patient‐years of exposure [estimated rate ratio 3.74 (95% CI 2.28; 6.13); P < 0.001]. IDegLira was generally well tolerated. The rates of serious adverse events were 20.3 and 8.0 per 100 patient‐years of exposure with IDegLira and placebo, respectively, without obvious patterns in the type of events.Conclusions IDegLira can be used in people uncontrolled with sulphonylurea ± metformin to improve efficacy with a safety profile in line with previous DUAL trials.

The Clinical Impact of GLP-1 Receptor Agonists in Type 2 Diabetes: Focus on the Long-Acting Analogs

“…[17][18][19][20][21][22] In a 52-week comparison of IDegLira with insulin degludec or liraglutide alone, 22 the mean HbA 1c at 52 weeks was reduced by 1.84% in the IDegLira group, 1.40% in the insulin degludec group, and 1.21% in the liraglutide group. Seventy-eight percent of the patients on IDegLira achieved an HbA 1c of <7% compared with 63% of patients receiving insulin degludec and 57% of those receiving liraglutide.…”

Methodological concerns with the meta-analysis comparing insulin degludec/liraglutide and insulin glargine/lixisenatide

“…The FPG at baseline was 7.3/ 7.4 mmol/L in one trial [6], whereas baseline FPG values ranged from 8.9 to 9.9 mmol/L in the other two IGlarLixi trials [3,4] and all the IDegLira trials [2,5,[7][8][9]. Furthermore, the target FPG was 4.4-5.6 mmol/L in all the IGlarLixi trials, whereas it was 4.0-5.0 mmol/L in all but one of the IDegLira trials.…”

A review of the efficacy and safety of the finished fixed-ratio combination of insulin degludec and liraglutide in the treatment of type 2 diabetes mellitus

“…Терапевтическая эффективность ИДегЛира в качестве дополнительной терапии при неэффективности перо-ральных сахароснижающих препаратов или других аго-нистов рецепторов ГПП-1 или базального инсулина изу-чалась в ходе 7 клинических рандомизированных муль-тинациональных исследований III фазы: DUAL-I [11], -II [6], -III [19], -IV [26], -V [18], -VI [14], -VII [5], а также в течение 26 недель продления исследования DUAL-I [12].…”

“…и количества человек, достигших целево-го уровня HbA 1с < 7,0 и ≤ 6,5% (р < 0,001) [26]. Однако в группе плацебо отмечалось снижение массы тела в срав-нении с группой ИДегЛира (-1,0 против +0,5 кг, р < 0,001).…”

“…Однако в группе плацебо отмечалось снижение массы тела в срав-нении с группой ИДегЛира (-1,0 против +0,5 кг, р < 0,001). Средняя доза ИДегЛира по окончании исследования составила 28 шагов дозы (что соответствует дозе инсули-на деглудек 28 ЕД и лираглутида 1 мг), средняя доза плацебо -44 шага дозы [26].…”