In this study, patients showed significant weight gains with the sulphonyl ureas and insulin (means of 5 kg and 7 kg, respectively), but not with metformin (1 kg gain). Also, hypoglycaemic reactions or 'hypos', abnormally low levels of blood glucose leading to tremors, cold sweats and headache accompanied by irritability, confusion and hallucinations, and ultimately resulting in convulsions and coma were least frequent with metformin. Glucose control deteriorated steadily over time with all treatments whether diet, sulphonylureas, metformin or insulin due to decreased pancreas islet cell function.
After four to five years of therapy, HbA1c levels rose to even higher values than before treatment (Ann Intern Med, 1996; 124: 136-45). However, sulphonyl ureas, metformin and insulin all reduced levels of HbA1c by 0.7-0.8 per cent more than diet alone.
In other studies, troglitazone reduced HbA1c by 0.5 per cent more than diet alone (Diabetes Care, 1996; 19: 151-6) whereas acarbose reduced HbA1c by 0.55-0.90 per cent (Ann Intern Med, 1994; 121: 928-35; Am J Med, 1995; 98: 443-5). However, these trials also questioned the long term effectiveness of these drugs as well as their dangers.
The University Group Diabetes Program (UGDP) study, involving insulin and antidiabetes drugs, failed to prove that diabetes pills could prevent the long term complications of diabetes such as heart and kidney disease, and blindness (Diabetes, 1970; 19 [Suppl 2]: 813). Instead of preventing disease, it is likely that these drugs increase the risk of death due to cardiovascular disease (J Am Med Assoc, 1975; 231: 624).
Unlike insulin, oral hypoglycaemics are only somewhat effective in lowering blood sugar. They fail to adequately control blood sugar in 20-40 per cent of patients. But even if they work at first, they may later fail in as many as 30 per cent of patients per year (ADIS Health Science Press, 1984: 231).
After the UGDP report was released, two clinics that stopped using oral hypoglycaemics found no change in blood sugar in about one third to one half of patients who'd been taken off the drugs. This indicates that these patients didn't need the drugs in the first place (J Am Med Assoc, 1975; 231: 624). The remaining patients were able to lower their blood sugar with diet alone or with a combination of diet and insulin.
These results suggest that a majority of the diabetics who take oral hypoglycaemics could get along with only mild dietary changes and avoid the risk of premature heart disease.
The sulphonylurea chlorpropamide may cause dangerous, long lasting periods of low blood sugar. It may also produce breathing difficulties, drowsiness, muscle cramps, seizures, swelling of the face, hands or ankles, unconsciousness, water retention, or weakness that could be life threatening in those who tend to retain water, or who have congestive heart failure or cirrhosis of the liver
(Am Med Assoc, 1983: 1045. For these reasons, the World Health Organization recommends that this drug not be used by people aged 60 years or older. It is supplied in the UK on a named patient only basis to be taken only by the patient named on the scrip and is not recommended for general prescription.
Acetohexamide, another sulphonyl urea, is eliminated from the body mainly by the kidneys. Since kidney function decreases steadily with age, there is a possibility that toxic amounts of this drug may accumulate in older people.