Pills for Diabetes

Three years ago there was not a single antidiabetic drug that U.S. doctors could prescribe generally, and of two under test, one (carbutamide) was dropped for fear of liver damage. Diabetes victims were slaves to insulin and the needle. Last week 515 experts gathered in Manhattan under the auspices of the New York Academy of Sciences for the second symposium in seven months on the several drugs now being promoted: three on general prescription,* three being tested on patients under research safeguards./-

On some points the researchers purred harmoniously; on others they disagreed violently. Main points of agreement:

P: Drugs do not release patients from the need to control their weight and adhere strictly to a prescribed diet.

P:The oral drugs do not always take the place of insulin, though they may reduce the need for injections by either 1) stimulating the release of natural insulin from a sluggish pancreas, or 2) increasing the effectiveness of natural or injected insulin.

P:Sulfonylureas are strictly for the stable diabetic whose disease has become evident in middle life. They are not for the unpredictable up-and-down group that includes nearly all whose disease began in childhood. Young people, wrongly treated by inexpert physicians, have suffered severely as a result.

P:Tolbutamide is the safest of the sulfonylureas. (A good thing, since 500,000 of the known 1,500,000 U.S. diabetics are taking it regularly.)

Side Effects. About there the agreement ended. Dr. Robert F. Bradley Jr. of Boston's famed Joslin Clinic, reporting on 1,000 patients intensively studied, said tolbutamide gave good control in 55% and fair control in 14%. For chlorpropamide and metahexamide, the proportions were about the same--but not the patients: some who did poorly on tolbutamide responded to one of the other drugs, and a few who failed on two responded to the third. There was no denying that side effects (skin rashes, nausea, vomiting, heartburn) were more common with chlorpropamide and metahexamide, and there were a few cases of liver damage. Concluded cautious Dr. Bradley: "Further cautious trial appears justified."

As for the biguanides, the Joslin Clinic's Dr. Leo P. Krall conceded (after trial in 244 patients) that they "are capricious unless the physician uses them with special understanding." But he insisted that DBI, given along with reduced doses of insulin, has helped some unstable diabetics to lead a more normal life than they could when they took insulin several times a day. Main trouble: there is a narrow margin of safety between the DBI dose needed to control the blood sugar level and the dose that may produce side effects, so treatment in severe cases should begin in a hospital.

Horse Race. Dr. Henry Dolger of Manhattan's Mount Sinai Hospital would have none of these fine distinctions, made a free-swinging attack on all the drugs except tolbutamide. The extra potency of chlorpropamide and metahexamide. he charged, "is associated with an inexcusable increase in serious side effects . . . This has degenerated into a horsepower race." Other Dolger slashes: "A purported advantage of more prolonged effects from chlorpropamide has been a disadvantage in my opinion [by dropping the blood sugar too low for too long], because an elderly arteriosclerotic patient may suffer irreversible brain damage from such a 'beneficial' effect . . . Combination therapy with either sulfonylurea compounds or DBI and insulin has proved useless--also, it is anxiety-producing for both patients and physicians . . . [I] have not been able to confirm the claim that DBI will abolish, reduce, or stabilize the insulin requirements in a single insulin-treated patient."

Though Dr. Dolger was in the minority, it was enough to send a disappointed diabetic patient's blood sugar up--and his blood pressure too.

*Tolbutamide (Upjohn Co.'s Orinase) and chlorpropamide (Charles Pfizer & Co.'s Dia-binese), both belonging to the chemical family of sulfonylureas, and a newly available biguanide, phenethylbiguanide (U.S. Vitamin Corp.'s DBI).

/-Metahexamide (Eli Lilly & Co.'s Melonex, Upjohn's Euglycin), another sulfonylurea, and two members of the biguanide family--n-amyl (DBB) and n-butyl (DBV).

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