Solosamet SR Mechanism of Action

Pharmacology: Pharmacodynamics: Clinical Efficacy/Clinical Studies: A 16-week, double-blind, double-dummy, two-arm, parallel group study was conducted to compare the efficacy and safety of glimepiride/metformin SR 2/500 mg daily (OD) versus glimepiride/metformin 1/250 mg twice daily (BID) in patients with type 2 diabetes mellitus (T2DM). 10 Patients (N=207) were randomized to either glimepiride/metformin SR OD administered with the morning meal or glimepiride/metformin BID administered with the morning and evening meal. The primary objective was to demonstrate equivalence, based on the mean change in glycated hemoglobin (HbA1c) from baseline to endpoint (week 16) between glimepiride/metformin SR 2/500 mg OD and glimepiride/metformin 1/250 mg BID.
HbA1c at baseline was 8.05% in glimepiride/metformin SR OD group and 8.13% in glimepiride/metformin BID group. At study end, HbA1c was decreased by 0.59% (adjusted mean=0.61%) to a mean value of 7.47% for glimepiride/metformin SR OD and by 0.67% (adjusted mean=0.65%) to 7.46% for glimepiride/metformin BID.
Difference in adjusted mean between the two treatment groups was 0.04% with (-0.16%, 0.24%) of its confidence interval. Therefore, 95% two-sided confidence interval for the difference in change of HbA1c existed within the equivalence range (-0.5%, +0.5%).
Regarding nocturnal hypoglycemia there was no significant difference between the two treatment groups. Likewise, statistical significance was not observed between treatment groups based on the frequency of hypoglycemia. No statistical significance was observed between the two groups with regard to adverse events, although the occurrence was lower in the glimepiride/metformin SR OD treatment group.
Pharmacokinetics: Glimepiride pharmacokinetics (Tmax and AUC) after meal was similar between a sustained-release formulation of Glimepiride + Metformin HCl (Solosamet SR) 2/500 mg and an immediate-release formulation of single Glimepiride + Metformin HCl (Solosamet) 2/500 mg or BID. Glimepiride + Metformin HCl (Solosamet) 1/250 mg. Meanwhile, metformin tmax was delayed in sustained-release formulation compared to immediate-release formulation, but its elimination half-life was not prolonged.
The extent of metformin exposure after meal was lower in sustained-release formulation than in immediate-release formulation and its B.I.D. treatment in divided doses by 14% and 23% on average respectively. This effect on exposure is not considered clinically significant as there was no significant difference in safety between treatment groups.
An open label, 3-period, 3-treatment, 3-way crossover study was conducted in 12 healthy Korean male subjects to evaluate the pharmacokinetic and safety profiles of Glimepiride + Metformin HCl (Solosamet) and Glimepiride + Metformin HCl (Solosamet SR) tablets.
Subjects were randomized to one of 3 treatment arms (Group A, B or C). Subjects in group A received a single Glimepiride + Metformin HCl (Solosamet SR) 2/500 mg after breakfast. Group B received a single Glimepiride + Metformin HCl (Solosamet) 2/500 mg after breakfast. Group C received Glimepiride + Metformin HCl (Solosamet) 1/250 mg after breakfast and 12 hours later after dinner. There was a 7-day washout period between each treatment period.
Pharmacokinetic parameters: (See Table 1.)

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