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FDA issues warning on diet-drug combination
THE LANCET
SCIENCE AND MEDICINE
NEWS FDA issues warning on diet-drug combination n July 8, the US Food and Drug carcinoid or ergotamine toxicity. Administration warned physiThe valve damage seen in these cians that the popular diet-drug conditions is characterised by a combination of fenfluramine and glistening white macroscopic appearphentermine (fen/phen) might cause ance, and the damage may be related valvular heart disease in otherwise to high circulating serotonin concenhealthy women. Patients should not trations. Microscopically, endothelial stop the drugs, but should be monifibrosis is seen, which causes the tored, says the FDA. valve to malfunction. The agency has And according to received 33 reports Connolly, the same of abnormalities of type of valve damage mitral, aortic, and was seen in tricuspid valves in the women taking women aged 30 to 72 fen/phen. The nine years, who took the additional cases drugs for 12 months reported to the FDA on average. James had similar patholoBilstad, director of gies, says Bilstad. the FDA evaluation All cases had regurgitant valves Serotonin could be center for endocrino- see www.mayo.edu/news/ the culprit since logic drugs, says that both fenfluramine a link has not been established, but and phentermine raise serotonin the agency thought a warning was concentrations. warranted. Bilstad and Connolly say that there The New England Journal of seems to be no specific dose or duraMedicine lifted its embargo by weeks tion of drug use that triggers the valve to allow researchers from the Mayo problems, and that it is not clear Clinic and MeritCare Medical Center whether one, both, or either of the (Fargo, ND) to release their case drugs is responsible. The drugs are studies of 24 of the 33 patients. The not approved by FDA for combinapatients, who had no previous cardiac tion use, and neither is approved for disease, were evaluated for routine use longer than a few weeks. clinical concerns. Heidi Connolly, Phentermine was approved in 1959 Mayo’s consultant in cardiologic disand fenfluramine in 1973, but combieases, found that the women had nation use first became popular in the damage akin to that seen in malignant early 1990s, says Bilstad. Science Photo Library
O
Despite lack of FDA approval, the combination is legal for off-label use. The agency cannot force manufacturers to conduct long-term studies, so it is talking with the one fenfluramine maker, Wyeth-Ayerst, and the many phentermine makers, about changing labelling to warn of the possible association. The agency is also asking physicians to report fen/phen adverse events more thoroughly. Bilstad says he hopes the publicity will help to uncover any more existing cases—the Mayo study and the FDA warning were front-page news in the USA, where millions of people take antiobesity drugs. Valve damage has not been seen with dexfenfluramine (Redux), approved in 1996. But both Bilstad and Connolly indicate that the possibility cannot be ruled out as yet. About half of the 33 women affected also had pulmonary hypertension, which has already been reported as a side-effect of fenfluramine, phentermine, and dexfenfluramine (see Lancet, May 10, p 1374). Two users of the fen/phen combination are now suing the manufacturers of the two drugs and the makers of dexfenfluramine for concealing the drugs’ hazards. The lawsuit, filed on July 9, will seek class-action status on behalf of millions of consumers. Alicia Ault
Clues to the diagnosis of non-insulin-dependent diabetes in children
D
espite similar clinical presentations, children with youthonset non-insulin-dependent diabetes mellitus (NIDDM) have several different features compared with children with insulin-dependent diabetes mellitus (IDDM). Carla Scott and colleagues (University of Arkansas, AR, USA) report the characteristics at diagnosis of children (mean age 13·9 years) with NIDDM and compare
Vol 350 • July 19, 1997
them with IDDM patients matched for age, sex, and area of residence (Pediatrics 1997; 100: 84–91). A striking difference was found in body-mass index (BMI). 96% of NIDDM children had a BMI above the 85th percentile for age and the mean BMI was 35 kg/m2 . By contrast, the mean BMI was 20 kg/m2 in IDDM patients. Polyuria, polydipsia, and abdominal pain were similar in the groups. Acanthosis
nigricans was seen in 86% of NIDDM but no IDDM patient. The proportion of patients with moderate-to-large serum ketone concentrations did not differ between groups. Given the reported rise in paediatric NIDDM, the authors warn that age at diagnosis should not be the only diagnostic criteria to differentiate types of diabetes. K D Hopkins
189
SCIENCE AND MEDICINE
NEWS FDA issues warning on diet-drug combination n July 8, the US Food and Drug carcinoid or ergotamine toxicity. Administration warned physiThe valve damage seen in these cians that the popular diet-drug conditions is characterised by a combination of fenfluramine and glistening white macroscopic appearphentermine (fen/phen) might cause ance, and the damage may be related valvular heart disease in otherwise to high circulating serotonin concenhealthy women. Patients should not trations. Microscopically, endothelial stop the drugs, but should be monifibrosis is seen, which causes the tored, says the FDA. valve to malfunction. The agency has And according to received 33 reports Connolly, the same of abnormalities of type of valve damage mitral, aortic, and was seen in tricuspid valves in the women taking women aged 30 to 72 fen/phen. The nine years, who took the additional cases drugs for 12 months reported to the FDA on average. James had similar patholoBilstad, director of gies, says Bilstad. the FDA evaluation All cases had regurgitant valves Serotonin could be center for endocrino- see www.mayo.edu/news/ the culprit since logic drugs, says that both fenfluramine a link has not been established, but and phentermine raise serotonin the agency thought a warning was concentrations. warranted. Bilstad and Connolly say that there The New England Journal of seems to be no specific dose or duraMedicine lifted its embargo by weeks tion of drug use that triggers the valve to allow researchers from the Mayo problems, and that it is not clear Clinic and MeritCare Medical Center whether one, both, or either of the (Fargo, ND) to release their case drugs is responsible. The drugs are studies of 24 of the 33 patients. The not approved by FDA for combinapatients, who had no previous cardiac tion use, and neither is approved for disease, were evaluated for routine use longer than a few weeks. clinical concerns. Heidi Connolly, Phentermine was approved in 1959 Mayo’s consultant in cardiologic disand fenfluramine in 1973, but combieases, found that the women had nation use first became popular in the damage akin to that seen in malignant early 1990s, says Bilstad. Science Photo Library
O
Despite lack of FDA approval, the combination is legal for off-label use. The agency cannot force manufacturers to conduct long-term studies, so it is talking with the one fenfluramine maker, Wyeth-Ayerst, and the many phentermine makers, about changing labelling to warn of the possible association. The agency is also asking physicians to report fen/phen adverse events more thoroughly. Bilstad says he hopes the publicity will help to uncover any more existing cases—the Mayo study and the FDA warning were front-page news in the USA, where millions of people take antiobesity drugs. Valve damage has not been seen with dexfenfluramine (Redux), approved in 1996. But both Bilstad and Connolly indicate that the possibility cannot be ruled out as yet. About half of the 33 women affected also had pulmonary hypertension, which has already been reported as a side-effect of fenfluramine, phentermine, and dexfenfluramine (see Lancet, May 10, p 1374). Two users of the fen/phen combination are now suing the manufacturers of the two drugs and the makers of dexfenfluramine for concealing the drugs’ hazards. The lawsuit, filed on July 9, will seek class-action status on behalf of millions of consumers. Alicia Ault
Clues to the diagnosis of non-insulin-dependent diabetes in children
D
espite similar clinical presentations, children with youthonset non-insulin-dependent diabetes mellitus (NIDDM) have several different features compared with children with insulin-dependent diabetes mellitus (IDDM). Carla Scott and colleagues (University of Arkansas, AR, USA) report the characteristics at diagnosis of children (mean age 13·9 years) with NIDDM and compare
Vol 350 • July 19, 1997
them with IDDM patients matched for age, sex, and area of residence (Pediatrics 1997; 100: 84–91). A striking difference was found in body-mass index (BMI). 96% of NIDDM children had a BMI above the 85th percentile for age and the mean BMI was 35 kg/m2 . By contrast, the mean BMI was 20 kg/m2 in IDDM patients. Polyuria, polydipsia, and abdominal pain were similar in the groups. Acanthosis
nigricans was seen in 86% of NIDDM but no IDDM patient. The proportion of patients with moderate-to-large serum ketone concentrations did not differ between groups. Given the reported rise in paediatric NIDDM, the authors warn that age at diagnosis should not be the only diagnostic criteria to differentiate types of diabetes. K D Hopkins
189