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TREATMENT OF TYPE 2 DIABETES: A SOUND APPROACH BASED UPON ITS PATHOPHYSIOLOGY
Increased Lipolysis Impaired Insulin Secretion TZDs GLP-1 analogues DPP-IV Inhibitors Sulfonylureas TZDs Metformin TZDs TZDs Metformin Hyperglycemia Hyperglycemia Increased HGP Decreased Glucose Uptake
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UKPDS: Effect of SU & Metformin Rx on HbA1c
Median HbA1c (%) Time (years) 9 8 7 6 3 12 15 UKPDS: Effect of SU & Metformin Rx on HbA1c Conventional Glibenclamide Metformin 37% EXCESS GLYCEMIC BURDEN UKPDS 352: and , 1998
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UKPDS: Effect of SU & Metformin Rx on HbA1c
Median HbA1c (%) Time (years) 9 8 7 6 3 12 15 UKPDS: Effect of SU & Metformin Rx on HbA1c Conventional Glibenclamide Metformin 37% EXCESS GLYCEMIC BURDEN UKPDS 352: and , 1998
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DURABILITY OF GLYCEMIC CONTROL WITH SULFONYLUREAS
1 Glyburide Glyburide Glimepiride SU Glyburide GLY Alvarsson (n=39) SU Alvarsson (n=48) Gliclazide RECORD (n=272) Change in HbA1c (%) Glyburide Hanefeld (n=250) Charbonnel (n=313) -1 Gliclazide UKPDS (n=1,573) Chicago (n=230) ADOPT (n=1,441) PERISCOPE (n=181) Tan (n=297) -2 1 2 3 4 5 6 10 TIME (years) 4
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KAPLAN-MEIER PLOT OF SECONDARY FAILURE OF METFORMIN MONOTHERAPY (N=1051) BY CATEGORIES OF DURATION OF DIABETES AT METFORMIN INITIATION Brown et al, Diabetes Care 33: , 2010 0.2 0.4 0.6 0.8 1.0 12 24 36 48 60 Months on Metformin Percent of Individuals Experiencing Secondary Failure (A1c > 7.5%) 24-35 Months 18.4% year > 36 Months 21.9% year 12-23 Months 21.4% year 4-11 Months 17.7% year 0-3 Months 12.2% year
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Insulin – Mediated Glucose
METFORMIN DOES NOT IMPROVE INSULIN SENSITIVITY IN T2DM PATIENTS (N=20) IN THE ABSENCE OF WEIGHT LOSS Cusi and DeFronzo, JCEM 81: , 1996 1.0 - Insulin – Mediated Glucose Uptake (mg/kg min) 0.75 - 0.5 - 0.25 - 0 - Before After
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DURABILITY OF GLYCEMIC CONTROL WITH THIAZOLIDINEDIONES
1 Hanefeld (n=250) Chicago (n=232) Charbonnel (n=317) ADOPT (n=1,456) PERISCOPE (n=178) Rosenstock (n=115) RECORD (n=301) Tan (n=249) PIO Rosiglitazone Change in HbA1c (%) PIO ROSI PIO -1 PIO PIO -2 1 2 3 4 5 6 TIME (years) 7
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EFFECT OF THIAZOLIDINEDIONES ON INSULIN-MEDIATED GLUCOSE DISPOSAL
Miyazaki & DeFronzo, Diabetologia 44: 2210, 2001 Diabetes Care 24: 710, 2001 * * 10 8 NOGD mg/kg FFM•min 6 4 GOX Before PIO ROSI
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EFFECT OF TZD AND PLACEBO TREATMENT ON ISR IN RELATIONSHIP TO INSULIN RESISTANCE
1 IR 2500 2000 1500 1000 500 Before Rx After Rx * x * * ISR (AUC) Glucose (AUC) + Placebo Naïve Naïve + PIO Naïve + ROSI SU + Placebo SU + PIO
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