Repaglinide/metformin fixed-dose combination to improve glycemic control in patients with type 2 diabetes: an update

Figures & data

Figure 1 Mean changes in glycated hemoglobin (HbA_1c) levels from baseline in patients receiving repaglinide or metformin monotherapies or repaglinide + metformin combination therapy. Drawn from data of Moses et al, 1999.¹²

Table 1 Glycemic control in terms of HbA_1c levels from key studies involving the co-administration of repaglinide and metformin (loose combination) in patients with type 2 diabetes

Reference	Patient population	Overview of study design	Key efficacy findings
Moses et al^Citation12 and Moses et al^Citation20	Suboptimal glycemic control after 6 months of metformin monotherapy	4–5 months of treatment with: repaglinide + placebo (n = 29) placebo + metformin (n = 27) repaglinide + metformin (n = 27)	Mean HbA1c levels significantly reduced from baseline with repaglinide + metformin (P < 0.01); reductions with monotherapies not significant Reduction in HbA1c level with repaglinide + metformin significantly greater than those with monotherapies (P < 0.05 in each case), and reduction numerically greater than the sum of the effects for each monotherapy More patients in the repaglinide + metformin group (56%) achieved HbA1c target levels of < 7.0% than in the monotherapy groups (19% in each case)
Reboussin et al^Citation22	Suboptimal glycemic control with diet and exercise or with fewer than three OADs	16 weeks of treatment with: repaglinide (n = 44) repaglinide + metformin (n = 42)	Reductions in HbA1c levels from baseline significant for both groups (P < 0.001) Change from baseline in HbA1c level greater with repaglinide + metformin than with repaglinide monotherapy (P < 0.05)
Raskin et al^Citation21	Suboptimal glycemic control with OAD monotherapy or glyburide/metformin combination therapy	16 weeks of treatment with: repaglinide + metformin (n = 96) nateglinide + metformin (n = 96)	HbA1c reduction with repaglinide + metformin significantly greater than that for nateglinide + metformin (P < 0.001) More patients in the repaglinide + metformin group (59%) achieved HbA1c target levels of ≤ 7.0% than in the nateglinide + metformin group (47%)

Abbreviations: HbA_1c, glycated hemoglobin; OAD, oral antidiabetes drug.

Figure 2 Glycated hemoglobin (HbA_1c) values by study visit for repaglinide/metformin twice daily (BID) and three times daily (TID) fixed-dose combination regimens. Raskin P, Lewin A, Reinhardt R, Lyness W, for the repaglinide/metformin fixed-dose combination study group. Twice-daily and three-times-daily dosing of a repaglinide/metformin fixed-dose combination tablet provide similar glycemic control. Diab Obes Metab. 2009;11:947–952.²³ Reprinted with permission from John Wiley & Sons Inc.

Abbreviation: LOCF, last observation carried forward.

Figure 3 Fasting plasma glucose (FPG) values by study visit for repaglinide/metformin twice daily (BID) and three times daily (TID) fixed-dose combination regimens. Raskin P, Lewin A, Reinhardt R, Lyness W, for the repaglinide/metformin fixed-dose combination study group. Twice-daily and three-times-daily dosing of a repaglinide/metformin fixed-dose combination tablet provide similar glycemic control. Diab Obes Metab. 2009;11:947–952.²³ Reprinted with permission from John Wiley and Sons Inc.

Abbreviation: LOCF, last observation carried forward.

Figure 4 Glycated hemoglobin (HbA_1c) values by study visit for repaglinide/metformin and rosiglitazone/metformin twice daily fixed-dose combination regimens. Raskin P, Lewin A, Reinhardt R, Lyness W; for the repaglinide/metformin fixeddose combination study group. Twice-daily dosing of a repaglinide/metformin fixeddose combination tablet provides glycemic control comparable to rosiglitazone/metformin tablet. Diab Obes Metab. 2009;11:865–873.²⁴ Reprinted with permission from John Wiley & Sons Inc.

Abbreviation: LOCF, last observation carried forward.

Figure 5 Fasting plasma glucose (FPG) values by study visit for repaglinide/metformin and rosiglitazone/metformin twice daily fixed-dose combination regimens. *P < 0.05 for between-group differences in change in FPG. Raskin P, Lewin A, Reinhardt R, Lyness W; for the repaglinide/metformin fixed-dose combination study group. Twice-daily dosing of a repaglinide/metformin fixed-dose combination tablet provides glycemic control comparable to rosiglitazone/metformin tablet. Diab Obes Metab. 2009;11:865–873.²⁴ Reprinted with permission from John Wiley & Sons Inc.

Abbreviation: LOCF, last observation carried forward.

Panel Key features of the prescribing information for PrandiMet^® in the USA¹⁵

Contraindications

Patients with/receiving: renal impairment metabolic acidosis, including diabetes ketoacidosis both gemfibrozil and itraconazole

Warnings and precautions

Assess renal function before initiating therapy and at least annually thereafter, and verify as normal Temporarily discontinue therapy in patients receiving iodinated contrast for radiological studies Do not use in patients with hepatic impairment Warn patients against excess alcohol intake Do not use in combination with NPH insulin Co-administration with gemfibrozil is not recommended Initiate at the lowest available dose in patients naïve to meglitinide therapy Measure hematological parameters annually to assess vitamin B12 status Discontinue use and temporarily initiate insulin if glycemic control deteriorates during periods of stress or if there is decreased intake of fluids and food (eg, infection, surgery) There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with this or any other oral antidiabetes drug

Note: Information is applicable only to treatment within the USA.

Abbreviation: NPH, neutral protamine Hagedorn.

Moses R Slobodniuk R Boyages S Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes Diabetes Care 1999 22 119 124 10333912

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Moses R Achieving glycosylated haemoglobin targets using the combination of repaglinide and metformin in type 2 diabetes: a reanalysis of earlier data in terms of current targets Clin Ther 2008 30 552 554 18405794

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Reboussin DM Goff DC Lipkin EW The combination and nutritional treatment of late-onset diabetes mellitus (CONTROL DM) trial results Diabet Med 2004 21 1082 1089 15384954

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Raskin P Klaff L McGill J for the repaglinide vs nateglinide metformin combination study group Efficacy and safety of combination therapy: repaglinide plus metformin versus nateglinide plus metformin Diabetes Care 2003 26 2063 2068 12832314

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Raskin P Lewin A Reinhardt R Lyness W for the repaglinide/metformin fixed-dose combination study group Twice-daily and three-times-daily dosing of a repaglinide/metformin fixed-dose combination tablet provide similar glycemic control Diab Obes Metab 2009 11 947 952

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Raskin P Lewin A Reinhardt R Lyness W for the repaglinide/metformin fixed-dose combination study group Twice-daily dosing of a repaglinide/metformin fixed-dose combination tablet provides glycemic control comparable to rosiglitazone/metformin tablet Diab Obes Metab 2009 11 865 873

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Novo Nordisk Inc Prescribing information for PrandiMet (repaglinide and metformin HCl) tablets 2008 www.prandimet.com Accessed December 10, 2009

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