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Efficacy and safety of different basal and prandial insulin analogues for the treatment of type 2 diabetes: a network meta-analysis of randomized controlled trials

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Abstract

Aim

The aim of the present network meta-analysis is to assess the efficacy and safety across different long and short-acting analogs for the treatment of type 2 diabetes.

Methods

A PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases search (20th May, 2020) for all trials with a duration ≥24 weeks comparing an analogue with another or human insulin was performed. Indirect comparisons were performed by NMA choosing glargine U100 and human regular insulin, as the reference for long- and short-acting analogues, respectively. Primary endpoints were HbA1c at 24, 52, and 104 weeks. The weighted difference in means (WDM) and Mantel-Haenzel Odds Ratio [MH-OR] with 95% Confidence Intervals (CI) were calculated for categorical and continuous variables, respectively.

Results

Fifty trials (n = 43) and 7 for basal and prandial analogues, respectively, enrolling 25,554 and 3184 patients with type 2 and 1 diabetes, respectively, were included. At NMA, detemir was less effective than glargine U-100 at 52 weeks. A significant reduction of 24-week HbA1c (WMD [IC]: −0.10 [−0.17, −0.03]%); and risk of total (MH-OR [IC]: 0.80 [0.70, 0.91]), and nocturnal hypoglycemia (MH-OR [IC]: 0.57 [0.45, 0.73]) was observed for basal analogues versus NPH insulin. At NMA, glargine U300 and degludec were associated with a significant reduction in the risk of nocturnal hypoglycemia. No significant differences across different short-acting insulin were observed.

Conclusions

This paper supports the use of long-acting analogues, rather than NPH insulin, as basal insulin for the treatment of type 2 diabetes, without any preferences for any individual long-acting analogue over the others. The evidence on short acting analogues is limited.

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This research was performed as a part of the institutional activity of the unit, with no specific funding. All expenses, including salaries of the investigators, were covered by public research funds assigned to the unit.

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  1. Diabetology, Careggi Hospital, University of Florence, Florence, Italy

    Edoardo Mannucci & Matteo Monami

  2. University of Florence, Florence, Italy

    Edoardo Mannucci, Chiara Caiulo, Lara Naletto & Giuseppe Madama

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M.M. and E.M. were involved in design, data collection, analysis, writing paper. L.N. and C.C. were involved in paper revision, data collection.

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Correspondence to Matteo Monami.

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E.M. has received consultancy fees from Merck and Novartis speaking fees from Astra Zeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Eli-Lilly, Merck, Novo Nordisk, Sanofi, and Novartis and research grants from Merck, Novartis, and Takeda. C.C. and L.N. have no relevant conflicts of interest to declare. M.M. has received speaking fees from Astra Zeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Eli-Lilly, Merck, Novo Nordisk, Sanofi, and Novartis and research grants from Bristol Myers Squibb. All the authors approved the final version of this paper. M.M. is the person who takes full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the paper.

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Mannucci, E., Caiulo, C., Naletto, L. et al. Efficacy and safety of different basal and prandial insulin analogues for the treatment of type 2 diabetes: a network meta-analysis of randomized controlled trials. Endocrine 74, 508–517 (2021). https://doi.org/10.1007/s12020-021-02889-6

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