The recent summary of the NICE guidance is said to be designed to prevent or delay the progression from “pre-diabetes” to type 2 diabetes (T2DM) in people at high risk. (1) However, the recommendations seem to focus on obesity rather than type 2 diabetes or indeed pre-diabetes.
The NICE guidelines recommend Orlistat (Xenical) be prescribed to people with a BMI of 28.0 or more as part of an overall plan for managing obesity. This is surprising considering the recent Important drug warning for Xenical (May 2012) issued in the USA which highlights the dangers of Orlistat (Xenical)
The revised warnings and recommendations include updated information on potential renal effects of Orlistat (xenical) including cases of oxalate nephrolithiasis, acute nephropathy with renal failure after treatment with Orlistat (Xenical). It is recommended that renal function be monitored when prescribing Orlistat (Xenical) to patients at risk of renal impairment. Increased urinary oxalate, and cholelithiasis is also a concern. Gastro intestinal effects such as bleeding, although not serious, have also been observed. It is also recommended that hypothyroidism should be excluded before prescribing Orlistat. Orlistat is now considered inadvisable in pregnancy. (2) (3)
There have also been previous reports (2010) of hepatic failure observed with the use of Orlistat (Xenical) in postmarketing surveillance with some of these cases resulting in liver transplant or death. (4)
Even without these drug warnings Orlistat list side effects including: oily leakage from rectum, flatulence, faecal urgency, liquid or oily stools, faecal incontinence, abdominal distension and pain (gastro-intestinal effects minimised by reduced fat intake) (5) All in a bid to lose fat from the diet and lose weight!
Isn’t patient safety the first priority? Whilst such efforts are made to prevent diabetes, people are at increased risk of suffering iatrogenic disease. How can this ever be a good idea?
The recommended diet for T2DM is high in carbohydrates, how can normoglycaemia possibly be achieved on such a diet? Chronic hyperinsulinaemia in response to high carbohydrate consumption potentially leads to beta-cell exhaustion. The concomitant low fat recommendations, not only reduces satiety - which can lead to overeating. It also means the body may not receive the vital nutrients of essential fats needed for homeostasis.
Past studies of newly diagnosed diabetics although carried out in the 1970s and 80s seem to be highly relevant in current diabetes prevention.
Grey and Kipnis (1971) (6) have shown that when obese patients are put on a carbohydrate-restricted diet the fasting plasma insulin level falls and rises again when a high carbohydrate, isocaloric diet is substituted, without any change in weight. Further, Rudnick and Taylor (1965) (7) reported improvement in carbohydrate tolerance and increased insulin responses to glucose in obese and non-obese diabetics after four months on a carbohydrate-restricted diet.
A 1973 UK study of two hundred newly diagnosed, overweight diabetics (T2DM) concluded that control of diabetes in obese patients who respond to diet alone is due to carbohydrate restriction rather than to weight loss. This result was achieved in 80% of the participants. A highly significant statement regarding this research was – ‘They did not start drug treatment until it was clear that diet alone had failed, which was usually after at least four months’. (8) This study was led by the late Professor David Pyke, a world renowned diabetologist at Kings College Hospital. These studies, amongst others, were examples of true clinical excellence.
A 1979 study found the haemoglobin A1c (HBA1c) blood test may also be a useful predictor of those patients likely to respond to diet alone and those likely to require treatment with an oral hypoglycaemic agent. (9) This suggestion has only very recently been implemented by the World Health Organisation WHO. In January 2011, a WHO expert consultation regarding the diagnosis of diabetes, recommended the acceptability of glycated haemoglobin (HbA1c), as an additional test to diagnose T2DM. (10)
Several more recent randomised trials have also shown that modest weight loss and physical activity can greatly reduce the risk of T2DM. (11)(12)(13)(14)(15)
As I have stated before in the BMJ in a recent rapid response. (16) How can the basic human need for proper and consistent nutrition matched by appropriate exercise be a priority in diabetes prevention, when commercial interests are touting for a lucrative solution, be it drugs or slimming products? The undeniable international commercial interest in type 2 diabetes continues to be a massive barrier to prevention of this lifestyle disorder.
T2DM will bring health services to their knees around the world. The fast tracking of drug treatments before adequate preventative measures have been implemented seems inadvisable. The overreliance on pharmaceutical treatments will add a further epidemic of iatrogenic disease if we do not clarify these issues.
(1) The Risk identification and interventions to prevent type 2 diabetes in adults at high risk: summary of NICE guidance BMJ2012;345:e4624
(2) http://www.gene.com/gene/products/information/xenical/ accessed 21 July 2012
(3) Reference ID: 3074639 1 Warnings and precautions Xenical www.accessdata.fda.gov/drugsatfda_docs/label/2012/020766s029lbl.
(4) Important changes in the prescribing information of Xenical (Orlistat) September 2010
http://www.gene.com/gene/products/information/xenical/ accessed 21 July 2012
(5) http://www.medicinescomplete.com/mc/bnf/current/73511.htm accessed 22 July 2012 BNF No 63 March 2012 Orlistat additional information
(6) Grey N. and Kipnis, D. M. (1971). New England Journal of Medicine,
(7) Rudnick, P. A., and Taylor, K. W. (1965). British Medical Journal, 1,1225.
(8) Effect of Carbohydrate Restriction in Obese Diabetics: Relationship of Control to Weight Loss J. R. Wall, D. A. Pyke, W. G. Oakley British Medical Journal, 1973, 1, 577-578
(9) D M Fraser, A F Smith, R S Gray, D Q Borsey, M E Sinclair, B F Clarke, L J P Duncan Glycosylated haemoglobin concentrations in newly diagnosed diabetics before and during treatment British Medical Journal, 1979, 1, 979-981
(10) Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes
Mellitus Abbreviated Report of a WHO Consultation WHO/NMH/CHP/CPM/11.1 2011
(11) Gillies CL, Abrams KR, Lambert PC, Cooper NJ, Sutton AJ, Hsu RT, et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ2007;344:299.
(12) Eriksson KF, Lindgarde F. Prevention of type 2 (non-insulin-dependent) diabetes mellitus by diet and physical exercise. The 6-year Malmo feasibility study. Diabetologia1991;34:891-8.
(13) Pan X, Li G, Hu Y, Wang J, Yang W, An Z, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. Diabetes Care1997;20:537-44.
(14) Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:1343-50.
(15) Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med2002;346:393-403.
(16) Re: Should we screen for type 2 diabetes: Yes | BMJ
www.bmj.com/content/345/bmj.e4514/rr/594470 (rapid response) Jane E Collis.