Rosiglitazone amplifies the benefits of lifestyle intervention measures in long‐standing type 2 diabetes mellitus

Reynolds, L. Raymond; Konz, Elizabeth C.; Frederich, Robert; Anderson, James W.

doi:10.1046/j.1463-1326.2002.00207.x

Cited by 38 publications

(29 citation statements)

References 28 publications

(44 reference statements)

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“…The advantage of MET over INS, sulfonylureas, and thiazolidinediones is the absence of weight gain despite improvements in glycemic control, although investigators have shown that weight gain can be avoided with thiazolidinediones when aggressive lifestyle interventions are implemented (33). Of interest is that subjects in this study did not gain weight when TGZ was added to dual treatment with INS ϩ MET, even though the HbA 1c level improved from 7.0 to 6.1%.…”

Section: Level (A) Weight (B) and Total Daily Ins Dose (C) In Instrmentioning

confidence: 85%

Improved Glycemic Control Without Weight Gain Using Triple Therapy in Type 2 Diabetes

2004

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OBJECTIVE -To evaluate the safety and effectiveness of triple therapy using insulin, metformin, and a thiazolidinedione following a course of dual therapy using insulin and metformin or insulin and a thiazolidinedione in type 2 diabetes.RESEARCH DESIGN AND METHODS -Twenty-eight type 2 diabetic subjects using insulin monotherapy (baseline HbA lc level 8.5%) who had been randomly assigned to insulin (INS) and metformin (MET) (INS ϩ MET, n ϭ 14) or INS and the thiazolidinedione troglitazone (TGZ) (INS ϩ TGZ, n ϭ 14) (dual therapy) for 4 months were given INS, MET, and TGZ (triple therapy: INS ϩ MET, add TGZ; or INS ϩ TGZ, add MET) for another 4 months. The INS dose was not increased. CONCLUSIONS -Triple therapy using INS, MET, and TGZ resulted in lower HbA lc levels and total daily insulin dose than during dual therapy. The use of triple therapy resulted in 100% of subjects achieving an HbA lc Ͻ7.0%, while decreasing the dose of INS. Weight gain was avoided when MET therapy preceded the addition of TGZ therapy. The addition of TGZ resulted in the greatest reductions in HbA lc levels and insulin dose. Triple therapy using INS, MET, and a thiazolidinedione (such as TGZ) can be a safe and effective treatment in type 2 diabetes. RESULTS Diabetes Care 27:1577-1583, 2004R esearch in the previous decade has conclusively demonstrated the benefit of improved blood glucose control in the prevention of diabetes complications (1,2). Efforts to advance our ability to achieve near normal glycemic control have resulted in an array of pharmaceutical interventions that not only lower blood glucose levels, but also have beneficial effects on comorbid conditions such as hypertension and hyperlipidemia. In the treatment of type 2 diabetes, health care providers have the option of using insulin (INS), sulfonylureas, thiazolidinediones, biguanides such as metformin (MET), and other oral agents to achieve treatment goals (3,4).MET has been shown to lower blood glucose levels by sensitizing the liver to the effects of insulin, thus suppressing hepatic glucose output. It also has mild effects on promoting glucose utilization (5,6). Thiazolidinediones, like troglitazone (TGZ), improve insulin sensitivity by enhancing insulin-mediated glucose disposal, resulting in reduced plasma insulin concentrations. Thiazolidinediones may also have modest effects on lowering hepatic glucose production (7-9). In addition, studies have shown that thiazolidinediones enhance ␤-cell responsiveness and may prolong ␤-cell survival (10,11). Several randomized, placebocontrolled studies have demonstrated the effectiveness of dual therapy using oral sulfonylureas or INS in combination with either MET or TGZ in lowering blood glucose levels in type 2 diabetic subjects (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Studies of the combined use of MET plus a thiazolidinedione have also shown improved glycemic control when compared with MET alone (23-26). Thiazolidinediones added to treatment with sulfonylureas and MET resulted in significant improvements in HbA 1c leve...

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Section: Level (A) Weight (B) and Total Daily Ins Dose (C) In Instrmentioning

confidence: 85%

Improved Glycemic Control Without Weight Gain Using Triple Therapy in Type 2 Diabetes

2004

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“…Our subjects were encouraged to maintain baseline levels of dietary intake, and food records revealed no change in dietary intake at the end of the study. Other studies have shown, however, that with caloric restriction, weight gain can be avoided when glycemic control is improved with thiazolidinediones (23,24).…”

Section: Adverse Eventsmentioning

confidence: 99%

The Effect of Rosiglitazone on Overweight Subjects With Type 1 Diabetes

Strowig

Raskin

2005

Diabetes Care

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OBJECTIVE -To evaluate the safety and effectiveness of rosiglitazone in the treatment of overweight subjects with type 1 diabetes.RESEARCH DESIGN AND METHODS -A total of 50 adult type 1 diabetic subjects with a baseline BMI Ն27 kg/m 2 were randomly assigned in a double-blind fashion to take insulin and placebo (n ϭ 25) or insulin and rosiglitazone 4 mg twice daily (n ϭ 25) for a period of 8 months. Insulin regimen and dosage were modified in all subjects to achieve near-normal glycemic control.RESULTS -Both groups experienced a significant reduction in HbA 1c (A1C) level (rosiglitazone: 7.9 Ϯ 1.3 to 6.9 Ϯ 0.7%, P Ͻ 0.0001; placebo: 7.7 Ϯ 0.8 to 7.0 Ϯ 0.9%, P ϭ 0.002) and a significant increase in weight (rosiglitazone: 97.2 Ϯ 11.8 to 100.6 Ϯ 16.0 kg, P ϭ 0.008; placebo: 96.4 Ϯ 12.2 to 99.1 Ϯ 15.0, P ϭ 0.016). Baseline measures of BMI (P ϭ 0.001), total daily insulin dose (P ϭ 0.002), total cholesterol (P ϭ 0.005), HDL cholesterol (P ϭ 0.00l), and LDL cholesterol (P ϭ 0.02) were predictors of improvement in A1C level only in the group treated with rosiglitazone. Total daily insulin dose increased in subjects taking placebo (74.0 Ϯ 33.8 to 82.0 Ϯ 48.9 units, P Ͻ 0.05 baseline vs. week 32), but it decreased slightly in subjects taking rosiglitazone (77.5 Ϯ 28.6 to 75.3 Ϯ 33.1 units). Both systolic blood pressure (137.4 Ϯ 15.6 vs. 128.8 Ϯ 14.8 mmHg, baseline vs. week 32, P Ͻ 0.02) and diastolic blood pressure (87.2 Ϯ 9.4 vs. 79.4 Ϯ 7.2 mmHg, P Ͻ 0.0001) improved in the group treated with rosiglitazone. The total incidence of hypoglycemia did not differ between groups.CONCLUSIONS -Rosiglitazone in combination with insulin resulted in improved glycemic control and blood pressure without an increase in insulin requirements, compared with insulin-and placebo-treated subjects, whose improved glycemic control required an 11% increase in insulin dose. Weight gain and hypoglycemia were similar in both groups at the end of the study. The greatest effect of rosiglitazone occurred in subjects with more pronounced markers of insulin resistance. Diabetes Care 28:1562-1567, 2005R esearch in the past decade has conclusively demonstrated that improved blood glucose control is of benefit in preventing the microvascular complications of diabetes (1,2). Although new insulin analogs and intensive insulin treatment regimens are effective in improving glycemic control, these treatments involve considerable effort and cost (3) and can result in weight gain and increased risk for severe and asymptomatic hypoglycemia (4). Faced with the challenge of balancing aggressive insulin replacement therapy against the risk for the potentially serious consequences of excessive weight gain and insulininduced hypoglycemia, investigators continue to search for treatments that address both the treatment of insulin deficiency as well as other metabolic abnormalities that are associated with diabetes (5).Insulin resistance, a metabolic abnormality common in type 2 diabetes, appears to be present in individuals with type 1 diabetes, as well. Although insuli...

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“…Rosiglitazone decreased both systolic and diastolic pressure [53,55] , suggesting that this drug could improve systolic and diastolic function. All of these findings indicate that in addition to improving insulin resistance in T2DM patients, rosiglitazone also has the beneficial effects on overall cardiovascular risk.…”

Section: Beneficial Effects Of Rosiglitazone On the Cardiovascular Symentioning

confidence: 98%

“…Mice with I/R injury 3 mg/kg per day po; pretreated for 14 d prior to I/R Reduced ratio of infarct size to ischemic area (area at risk) Cardioprotective effects of rosiglitazone against I/R injury were mediated via a PI3K/Akt/GSK-3α-dependent pathway [59] Reduced the occurrence ventricular fibrillation Attenuated cardiac apoptosis Increased levels of p-Akt and p-GSK-3α T2DM patients (n = 21) 4 mg/d; 6 mo Weight loss (first 12 wk) Rosiglitazone amplified some of the positive benefits of lifestyle intervention [55] Decreased waist circumference Decreased systolic and diastolic blood pressure Reduced HbA1c…”

Section: Beneficial Effects Of Rosiglitazone On the Cardiovascular Symentioning

confidence: 99%

PPARγ activator, rosiglitazone: Is it beneficial or harmful to the cardiovascular system?

Palee¹

2011

WJC

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Rosiglitazone is a synthetic agonist of peroxisome proliferator-activated receptor γ which is used to improve insulin resistance in patients with type Ⅱ diabetes. Rosiglitazone exerts its glucose-lowering effects by improving insulin sensitivity. Data from various studies in the past decade suggest that the therapeutic effects of rosiglitazone reach far beyond its use as an insulin sensitizer since it also has other benefits on the cardiovascular system such as improvement of contractile dysfunction, inhibition of the inflammatory response by reducing neutrophil and macrophage accumulation, and the protection of myocardial injury during ischemic/reperfusion in different animal models. Previous clinical studies in type Ⅱ diabetes patients demonstrated that rosiglitazone played an important role in protecting against arteriosclerosis by normalizing the metabolic disorders and reducing chronic inflammation of the vascular system. Despite these benefits, inconsistent findings have been reported, and growing evidence has demonstrated adverse effects of rosiglitazone on the cardiovascular system, including increased risk of acute myocardial infarction, heart failure and chronic heart failure. As a result, rosiglitazone has been recently withdrawn from EU countries. Nevertheless, the effect of rosiglitazone on ischemic heart disease has not yet been firmly established. Future prospective clinical trials designed for the specific purpose of establishing the cardiovascular benefit or risk of rosiglitazone would be the best way to resolve the uncertainties regarding the safety of rosiglitazone in patients with heart disease.

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Rosiglitazone amplifies the benefits of lifestyle intervention measures in long‐standing type 2 diabetes mellitus

Cited by 38 publications

References 28 publications

Improved Glycemic Control Without Weight Gain Using Triple Therapy in Type 2 Diabetes

Improved Glycemic Control Without Weight Gain Using Triple Therapy in Type 2 Diabetes

The Effect of Rosiglitazone on Overweight Subjects With Type 1 Diabetes

PPARγ activator, rosiglitazone: Is it beneficial or harmful to the cardiovascular system?

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