Will delayed release metformin provide better management of diabetes type 2?

Figures & data

Figure 1. Characteristics of the different formulations of metformin: delayed release compared with extended release and immediate release. GI: gastrointestinal; GLP-1: glucagon-like peptide-1; BID: twice a day; TID: three times a day.

Table 1. Main results (changes from baseline) of a 12-week, phase 2, placebo-controlled, dose-ranging study comparing metformin DR 600, 800, or 1,000 mg administered once daily; blinded placebo; or unblinded metformin XR 1,000 or 2,000 mg once-daily (reference) in patients with T2D (drug-naïve or after a 14–17 day wash-out) and an estimated glomerular filtration rate 60 ml/min/1.73 m². Adapted from data reported in reference.[13]

	Placebo N = 41	Met DR 600 mg N = 39	Met DR 800 mg N = 40	Met DR 1000 mg (*) N = 40	Met XR 1000 mg N = 40	Met XR 2000 mg N = 40
FPG (mg/dl) Median change at Week 4	−4	−11	−13	−18	−12	−25
FPG (mg/dl * week) Median change AUC 4–12 week	+ 4	−96	−108	−156	−98	−215
HbA1c (%, SE)	NA	−0.48	−0.45	−0.35	−0.45	−0.67
Placebo-subtracted LS mean change		(0.19)	(0.18)	(0.19)	(0.19)	(0.19)
Lactate (mmol/l) Mean change at Week 12	+ 0.16	+ 0.09	+ 0.06	+ 0.12	+ 0.33	+ 0.31
Gastrointestinal TEAEs (%)	7.3	12.8	17.5	15.0	17.5	12.5

Met DR: Meformin delayed release; Met XR: metformin extended release; FPG: fasting plasma glucose; AUC: area under the curve.

HbA1c: glycated haemoglobin; SE: standard error; LS: least square; TEAEs: treatment-emergent adverse events.

(*) In a preliminary phase 1 study, systemic exposure to metformin was reduced by 52% with metformin XR 1000 mg twice daily compared to Met XR 2000 mg once daily.

Buse JB, DeFronzo RA, Rosenstock J, et al. The primary glucose-lowering effect of metformin resides in the gut, not the circulation. Results from short-term pharmacokinetic and 12-week dose-ranging studies. Diabetes Care. 2016;39:198–205.

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