Insulin and its secretagogues are essential for some patients with type 2 diabetes (T2D) to maintain glycemic control (GC) . However, these drugs are inevitably accompanied by hypoglycemia. Avoiding severe hypoglycemia (SH) is essential considering its poor prognosis. This network meta-analysis aimed to find optimal hypoglycemic treatment regimens for T2D in terms of GC and SH. MEDLINE and EMBASE were used to identify trials comparing 2 or more treatments including insulins and/or SU/glinide and included both GC and SH in study outcomes. Treatment hierarchy was summarized as the surface under cumulative ranking probabilities (SUCRA) . There were 137 eligible trials from which 36 treatments were identified. Insulin plus (+) non-insulin drugs except for SU/glinide (others) had a higher SUCRA for changes in hemoglobin A1c (A1C) compared with only insulins (68.2±5.6% vs. 39.9±6.6%; P=0.01) although the difference in the SUCRA for SH was not significant (P=0.59) . Compared with only insulins, SU/glinide + others had a lower SUCRA for SH (42.4±5.8% vs. 58.5±3.4%, P=0.05) and comparable SUCRA for A1C change (P=1.00) . Cluster analysis indicated that premixed insulin + glucagon-like peptide-1 receptor agonist (Mix-ins+GLP1) consistently belonged to the high-efficacy group for A1C change and achievement of A1C<7.0% and ≤6.5% among the insulin + others therapies. Glinide + thiazolidinedione (TZD) was in groups with high efficacy in terms of A1C change and achievement of A1C<7.0% and high safety regarding SH among SU/glinide + others therapies. Results suggest that in T2D patients adjunctive use of non-insulin drugs (particularly, Mix-ins+GLP1) are recommended for further improving GC and that appropriate combinations of non-insulin hypoglycemic agents (particularly, glinide+TZD) are recommended to avoid SH and extend the time to treatment failure of non-insulin therapy.
S.Kodama: None. K.Kato: None. K.Watanabe: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. T.Sato: None. M.H.Yamada: None. M.Yamamoto: None. Y.Matsubayashi: None. H.Ishiguro: None. M.Iwanaga: None. K.Fujihara: None. T.Yamada: None.