TOLINASE Tablets are indicated as an adjunct to diet to lower the blood glucose in patients with noninsulin dependent diabetes mellitus (Type II) whose hyperglycemia cannot be satisfactorily controlled by diet alone. In initiating treatment for noninsulin-dependent diabetes, diet should be emphasized as the primary form of treatment.

Caloric restriction and weight loss are essential in the obese diabetic patient.

Proper dietary management alone may be effective in controlling the blood glucose and symptoms of hyperglycemia.

The importance of regular physical activity should also be stressed and cardiovascular risk factors should be identified and corrective measures taken where possible. If this treatment program fails to reduce symptoms and/or blood glucose, the use of an oral sulfonylurea or insulin should be considered.

Use of TOLINASE must be viewed by both the physician and patient as a treatment in addition to diet and not as a substitute for diet or as a convenient mechanism for avoiding dietary restraint.

Furthermore, loss of blood glucose control on diet alone may be transient thus requiring only short-term administration of TOLINASE. During maintenance programs, TOLINASE should be discontinued if satisfactory lowering of blood glucose is no longer achieved.

Judgments should be based on regular clinical and laboratory evaluations. In considering the use of TOLINASE in asymptomatic patients, it should be recognized that controlling the blood glucose in noninsulin-dependent diabetes has not been definitely established to be effective in preventing the long-term cardiovascular or neural complications of diabetes.

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Diabetes Mellitus, Non-Insulin-Dependent -- subclass of diabetes mellitus that is not insulin responsive or dependent; characterized initially by insulin resistance and hyperinsulinemia and eventually by glucose intolerance, hyperglycemia, and overt diabetes; type II diabetes mellitus is no longer considered a disease exclusively found in adults; patients seldom develop ketosis but often exhibit obesity.

Hyperglycemia -- Abnormally high BLOOD GLUCOSE level.

Symptoms -- An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.

Complication -- Any disease or disorder that occurs during the course of (or because of) another disease.

Complication Aspects -- Used with diseases to indicate conditions that co-exist or follow, i.e., co-existing diseases, complications, or sequelae.

Diabetes --

Diabetes Mellitus -- A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.

TOLINASE Tablets are contraindicated in patients with: 1) known hypersensitivity or allergy to TOLINASE; 2) diabetic ketoacidosis, with or without coma.

This condition should be treated with insulin; 3) Type I diabetes, as sole therapy.

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Hypersensitivity -- Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen.

Immediate hypersensitivity -- Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigen-antibody reaction and causes smooth muscle contraction and increased vascular permeability.

Diabetic Ketoacidosis -- A life-threatening complication of diabetes mellitus, primarily of TYPE 1 DIABETES MELLITUS with severe INSULIN deficiency and extreme HYPERGLYCEMIA. It is characterized by excessive LIPOLYSIS, oxidation of FATTY ACIDS, production of KETONE BODIES, a sweet smell to the breath (KETOSIS;) DEHYDRATION; and depressed consciousness leading to COMA.

comatose -- A profound state of unconsciousness associated with depressed cerebral activity from which the individual cannot be aroused. Coma generally occurs when there is dysfunction or injury involving both cerebral hemispheres or the brain stem RETICULAR FORMATION.

Diabetes Mellitus, Insulin-Dependent -- subtype of diabetes mellitus that is characterized by insulin deficiency; it is manifested by the sudden onset of severe hyperglycemia, rapid progression to diabetic ketoacidosis, and death unless treated with insulin; the disease may occur at any age, but is most common in childhood or adolescence.

The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin.

This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with noninsulin-dependent diabetes.

The study involved 823 patients who were randomly assigned to one of four treatment groups (DIABETES, 19 (supp.

2):747–830, 1970.) UGDP reported that patients treated for five to eight years with diet plus a fixed dose of tolbutamide (1.5 grams per day) had a rate of cardiovascular mortality approximately 2½ times that of patients with diet alone.

A significant increase in total mortality was not observed, but the use of tolbutamide was discontinued based on the increase in cardiovascular mortality, thus limiting the opportunity for the study to show an increase in overall mortality.

Despite controversy regarding the interpretation of these results, the findings of the UGDP study provide an adequate basis for this warning.

The patient should be informed of the potential risks and advantages of TOLINASE and of alternative modes of therapy. Although only one drug in the sulfonylurea class (tolbutamide) was included in this study, it is prudent from a safety standpoint to consider that this warning may also apply to other oral hypoglycemic drugs in this class, in view of their close similarities in mode of action and chemical structure.