Diabetes		Rosiglitazone and Metformin
Blood Sugar; Diabetes Mellitus; Non-Insulin Dependent Diabetes Mellitus; Type II Diabetes		Avandamet

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patients with type 2 diabetes continuing on glyburide therapy switched to metformin or given metformin as add on therapy to glyburide Data from

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® 7 pioglitazone hydrochloride Actos® 8 rosiglitazone malate Avandia® 9 acarbose Precose® Glucobay® 10 miglitol Glyset® The actions of sulfonylureas and meglitinides involve the stimulation of insulin secretion metformin suppresses hepatic glucose production the

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a growing realization by physicians and other caregivers that successful glycemic control for most patients will eventually require combination therapy

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will be seen However if drug B is added to drug A there is an improvement This concept can often be extended by the addition of drug C drug D

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is inadequately controlled with metformin alone adjunct therapy with rosiglitazone improves glycemic control insulin sensitivity and beta cell function Rosiglitazone and metformin have different mechanisms of action Dr Vivian Fonseca of Tulane University in New Orleans Louisiana and a multicenter

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additive effect as shown here combination of metformin and pioglitazone shown on the left of the graphic and combination of metformin and rosiglitazone shown on the right of the graphic Slide Metformin and Acarbose Combination Therapy Effect on HbA1c And finally metformin and alpha glucosidase inhibitors have been used in combination with some degree of success

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of drug class the baseline glycemic control significantly influences the overall magnitude of efficacy Data from Bloomgarden et al Table 1

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of Repaglinide to Metformin Similarly if we add repaglinide to patients taking metformin we will obtain an additional lowering of the FPG and HbA1c by 40 mg dL and 1 4 respectively Slide Mean Change in HbA1c and FPG at Week 26 Produced by Addition of Rosiglitazone to Sulfonylurea In the next graphic we see that if rosiglitazone RSG is added to sulfonylurea SU

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significantly and independently with plasma TGB 1 levels Table 4 and Figure 1 TGF β1 levels did not differ between men and women 21 77 ± 12 01 vs 21 85 ±9 90 respectively p=0 975 Figure 1 Correlation between FPG and TGF β1 Glucose is given in conventional units Correction Factor CF x CU = SI unit CF for glucose level is 0 055

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Sulfonylurea In the next graphic we see that if rosiglitazone RSG is added to sulfonylurea SU treated patients there is an additional lowering of HbA1c and FPG as you see over here Slide Mean Change in HbA1c and FPG at Week 16 Produced by Addition of Pioglitazone to Sulfonylurea And the same is true in the next graphic for pioglitazone Pio Note that in both of these

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A 52 year old Hispanic male with diabetes for 5 years and CHD S P PTCA 2 years ago presents for an initial visit His diabetes is controlled with metformin and rosiglitazone

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Both rosiglitazone Avandia® and metformin Glucophage® Fortamet® and others already have an established market share for managing Type 2 diabetes However recent clinical trials

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Both rosiglitazone Avandia® and metformin Glucophage® Fortamet® and others already have an established market share for managing Type 2 diabetes However recent clinical trials

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As shown in this study by Silvio Inzucchi comparing metformin and troglitazone the effect of the TZDs is on peripheral glucose disposal These two effects can be matched up very nicely Slide 32 Free Fatty Acid Levels Over Time Rosiglitazone Added to Metformin These data are taken from one of the rosiglitazone studies when rosiglitazone was added to the regimen of patients

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was a significant 32 relative risk reduction in the primary outcome in patients randomized to rosiglitazone compared to metformin and a 63 reduction in rosiglitazone compared to glyburide Figure 1 Independently adjudicated treatment failure was reached by 29 of patients in both the rosiglitazone and metformin groups and 22 in the glyburide group The secondary outcome was

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in the glyburide group The secondary outcome was reduced by a significant 34 in patients randomized to rosiglitazone compared to metformin and 62 in rosiglitazone compared to glyburide Figure 2 At 4 years significantly more patients in the rosiglitazone group achieved hemoglobin A1c <7 compared to both metformin and glyburide groups Figure 3 Maximal treatment

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compared to glyburide Figure 2 At 4 years significantly more patients in the rosiglitazone group achieved hemoglobin A1c <7 compared to both metformin and glyburide groups Figure 3 Maximal treatment effect on A1c was reached at 1 year in the rosiglitazone group compared to 4 months in both metformin and glyburide groups Tertiary outcomes such as insulin

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total cardiovascular events and investigator reported CHF in the rosiglitazone group Figures 4 and 5 However there were no differences in independently adjudicated CHF between groups Figure 6 These results provide evidence that rosiglitazone can slow progression to hyperglycemia to a greater extent than metformin or glyburide monotherapy The relative costs of these

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and leveling off thereafter With respect to adverse events there were a greater number of total cardiovascular events and investigator reported CHF in the rosiglitazone group Figures 4 and 5 However there were no differences in independently adjudicated CHF between groups Figure 6 These results provide evidence that rosiglitazone can slow progression to

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leveling off thereafter With respect to adverse events there were a greater number of total cardiovascular events and investigator reported CHF in the rosiglitazone group Figures 4 and 5 However there were no differences in independently adjudicated CHF between groups Figure 6 These results provide evidence that rosiglitazone can slow progression to hyperglycemia to

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