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© 2002 by the American Diabetes Association, Inc.
Letters: Comments and Responses |
Response to Lamotte et al.
1 From Policy Analysis Inc. (PAI), Brookline, Massachusetts
In the February 2002 issue of Diabetes Care, Lamotte et al. (1) present a provocative study of the cost-effectiveness of orlistat in obese type 2 diabetic patients. We suspect, however, that the authors have greatly overestimated the cost-effectiveness of this drug, due primarily to inappropriate parameter estimates.
First, the authors estimated the impact of reductions in HbA1c on the risks of macrovascular complications and death based on a finding from the Diabetes Control and Complications Trial (DCCT)—a 40% decrease in the risk of complications for every 10% reduction in HbA1c (2,3). The DCCT, however, included only type 1 diabetic patients, and this particular finding applied to microvascular complications only. Nevertheless, Lamotte et al. used this estimate—along with data from the U.K. Prospective Diabetes Study (UKPDS)—to project the risks of microvascular and macrovascular complications, as well as death, among type 2 diabetic patients (4). The authors estimated that a 0.46% absolute decrease in HbA1c, the assumed reduction with orlistat therapy (versus placebo), would reduce the annual risk of mortality by 27%, myocardial infarction (MI) by 29%, and stroke by 31% (5).
In our opinion, a better source with which to estimate these relationships is the UKPDS study of the association between glycemia and the complications of type 2 diabetes (6). In this study, a 1% absolute reduction in HbA1c was associated with 14% risk reductions in mortality and MI and a 12% reduction in stroke. Based on these data, estimated risk reductions with orlistat therapy (assuming a 0.46% absolute decrease in HbA1c) would have been substantially lower; 7% for mortality and MI, and 6% for stroke.
Second, they estimated the relationship between LDL cholesterol level and coronary events among type 2 diabetic patients using data from the Helsinki Heart Study (HHS), which was not adequately powered to accurately estimate treatment effects within subgroups (7,8). In this study, a 21.9-mg/dl reduction in LDL cholesterol was associated with a nominal 68% reduction in MI and cardiac death.
More reliable estimates can be found, we believe, in subgroup analyses from secondary prevention studies. In the Coronary Atherosclerosis and Recurrent Events (CARE) study, a mean 37-mg/dl decrease in LDL cholesterol was associated with a significant 25% reduction in coronary events (9). In the Scandinavian Simvastatin Survival Study (4S), an 
75- mg/dl reduction in LDL cholesterol was associated with a significant 57% reduction in major coronary events (10). These estimates are substantially lower than the HHS estimate (a reduction in coronary events of <1% per 1 mg/dl decrease in LDL cholesterol, versus 3% in the HHS), even though they occurred in the context of secondary prevention.
In summary, while it is impossible for us to calculate with certainty the effect that questionable parameter estimates had on their results, we believe it is quite likely that if the authors had used more appropriate data sources, their study would have yielded substantially higher cost-effectiveness ratios (i.e., they would have found orlistat to be substantially less cost-effective).
Acknowledgments
Policy Analysis Inc. (PAI) receives funding from Abbott Laboratories to conduct obesity-related research.
Footnotes
Address correspondence to Gerry Oster, Policy Analysis Inc. (PAI), Four Davis Ct., Brookline, MA 02445. E-mail: goster{at}pai2.com.
References
- Lamotte M, Nechelput M, Annemans L, Masure J, Lefever A: A health economic model to assess the long-term effects and cost-effectiveness of orlistat in obese type 2 diabetic patients. Diabetes Care 25: 303–308, 2002
[Abstract/Free Full Text]
- Diabetes Control and Complications Trial Research Group: The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes 44: 968–983, 1995[Abstract]
- Clark CM: The burden of chronic hyperglycemia. Diabetes Care 21 (Suppl. 3): C32–C34, 1998
- U.K. Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352: 854–865, 1998[Medline]
- Hollander PA, Kaplan RA, Elbein SC, Comstock J, Hirsch IB, Lucas CP, Kelley D, Lodewick PA, McGill J, Conavatchel W, Taylor T, Chung J, Weiss SR, Hauptman J, Crockett SE: Role of orlistat in the treatment of obese patients with type 2 diabetes: a 1-year randomized double-blind study. Diabetes Care 21: 1288–1294, 1998[Abstract]
- Stratton IM, Adler AI, Neil AW, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR: Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321: 405–412, 2000
[Abstract/Free Full Text]
- Koskinen P, Manitari M, Manninen V, Huttunen JK, Heinonen OP, Frick HM: Coronary heart disease incidence in NIDDM patients in the Helsinki Heart Study. Diabetes Care 15: 820–825, 1992[Abstract]
- Henry RR: Preventing cardiovascular complications of type 2 diabetes: focus on lipid management. Clin Diabetes 19: 113–120, 2001
[Abstract/Free Full Text]
- Goldberg RB, Mellies MJ, Sacks FM, Moye LA, Howard BV, Howard WJ, Davis BR, Cole TG, Pfeffer MA, Braunwald E: Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. Circulation 98: 2513–2519, 1998
[Abstract/Free Full Text]
- Haffer SM, Alexander CM, Cook TJ, Boccuzzi SJ, Musliner TA, Pederson TR, Kjekshus J, Pyorala K: Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels: subgroup analyses in the Scandinavian Simvastatin Survival Study. Arch Intern Med 159: 2661–2668, 1999
[Abstract/Free Full Text]
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