By Cameron Johnston, Special to DG News

Orlistat (Xenical, Roche), the anti-obesity drug that blocks fat absorption from the gut and leads to weight loss has been shown to raise high-density lipoprotein (HDL) and to lower serum triglycerides while leaving low-density lipoprotein (LDL) unchanged in obese Type 2 diabetics.

At the annual meeting of the European Association for the Study of Diabetes, being held in Brussels this week, researchers from Britain and Germany reported that the weight loss drug offers diabetics as much success at knocking off the kilos as it does the non-diabetic population. It also lowers serum cholesterol (LDL) and serum triglycerides, while raising HDL.

The degree of changes in lipid profiles appears to be largely dependent on the amount of weight loss, said Dr. John Wilding, a senior lecturer in medicine at the University of Liverpool, UK. Patients in a study who lost less than 5 percent of their body weight also experienced a 0.30 mmol/l change in LDL-C. Those who lost between 5-10 percent of their body weight had a 0.21 mmol change in LDL and those who lost more than 10 percent of body weight also saw a decline in cholesterol of 0.54 mmol/l.

"The effect of orlistat on total and LDL-C was independent of the magnitude of the weight loss," Dr. Wilding said.

In a study of 300 overweight patients with Type 2 diabetes who were being treated with sulfonylureas, patients randomized to receive orlistat had significant improvements in glycemic control compared with patients randomized to placebo. Besides decreases in fasting plasma glucose, the decline in HbA1c was 0.28 percent with orlistat vs 0.18 percent in the placebo group.

The researchers also noted a 23 percent reduction in the average daily dose of sulfonylureas required in the orlistat group vs a 9 percent reduction in the placebo group.

Curiously, placebo patients who lost between 5-10 percent of their body weight and who lost more than 10 percent of their body weight had greater decreases in HbA1c than did their counterparts in the orlistat group (1.15 percent and 2.29 percent, respectively).

Weight gain in the diabetic person is part of a vicious circle. People who gain weight are at risk of diabetes, hypertension and other complications, but the drugs used to treat the diabetes as well as the hypertension also promote weight gain. Fortunately, weight loss is part of a positive cascade of events.

Weight loss reduces the risk of diabetes enough so that some patients with impaired glucose can even return to normal glucose tolerance. Weight-loss also reduces blood pressure levels and stress on the cardiovascular system, and promotes a better balance in the patient's lipid profile.

While in practice it would be best for the clinician to deal with the diabetes first, Dr. Wilding said that's not always the easiest approach. In some patients, particularly those who have multiple risk factors, it might be more advisable to address the weight issue - which will also reduce cardiovascular and lipid stress, as well as the stress of the diabetes - before actively trying to treat the diabetes.

"One of the things we as physicians often forget is how hard it is to lose weight and how easy it is to gain weight," said Dr. Arya Sharma, a professor in the department of endocrinology and nephrology at the Free University of Berlin.

Indeed, he added, some of the drugs most commonly used by diabetics promote weight gain; insulin has been associated with a seven kg weight gain over 10 years, sulfonylureas are associated with a 2-5 kg gain, and metformin with a 1-2 kg gain. Those in the glitazone family have been associated with weight gains of up to 4-5 kg, in part, because better glycemic control, ironically, stimulates the appetite, so patients are likely to want to eat more.

Dr. Sharma said it is often advisable for hypertensive patients to switch from beta-blockers to an ACE inhibitor which is not associated with weight gain. Also, he advises, orlistat must be used under closely controlled circumstances. Licensing for the drug requires that it only be used when the patient has successfully lost 2.5 kg by dieting, and orlistat can only be continued if it can be shown that the patient has lost five percent of body weight over three months of use. It should not be continued if it does not meet the clinical requirements in that time, he said.