Weight loss, not drugs.

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VOL 49: SEPTEMBER • SEPTEMBRE 2003 Canadian Family Physician • Le Médecin de famille canadien 1077

Letters ^ Correspondance Letters ^ Correspondance

Weight loss, not drugs

I

would like to comment on a case report¹ regarding treatment of a patient with type 2 diabetes that was published in the June 2003 issue. In this case report, Dr Lockman pres- ents a case of a 56-year-old obese type 2 diabetic whose diabetes remained suboptimally controlled by 20 mg of glyburide and 2 g of metformin daily.

The patient was referred for lifestyle modification and was also started on repaglinide (4 mg three times daily). Subsequently, rosigli- tazone was added to the patient’s regi- men. The patient lost 20 kg during the ensuing few months, and his fast- ing glucose levels came down to 5 to 7 mmol/L from 17 to 30 mmol/L. These improvements were attributed to the use of four oral hypoglycemic agents in combination.

I would like to point out that both glyburide and repaglinide are insulin secretagogues, and their use in combination is neither recommended nor approved—nor does the combination have any pharmacodynamic appeal.

The use of two insulin secretagogues in combination is analogous to using two β-blockers. Although the patient’s diabetic control improved substantially, I strongly suspect the improvement was, in most part due to the weight loss, secondary to lifestyle modification, and due to the pancreatic cancer that was subsequently diagnosed.

I felt that I should point out this fact, as it would be inappropriate for your readers to get the impression that using a sulfonylurea along with another insulin secretagogue is good clinical practice.

—Hasnain M. Khandwala, MD

Saskatoon, Sask by mail

Reference

1. Lockman LE. Case report: treating type 2 diabetes. Using four oral hypoglycemic drugs. Can Fam Physician 2003;49:

775-6.

Response

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epaglinide is the first oral agent of the meglitinide class to become available for the treatment of type 2 diabetes and has a mechanism of B cell stimulation that differs from sulfonylureas. Repaglinide is chemically unrelated to sulfonylureas or any other currently available class of oral hypoglycemic agent. Rapid absorption and clearance of repaglinide make this a suitable choice for the management of meal-related glucose surges.¹ Also sulfonylureas do not need the presence of glucose to exert their effect, whereas repaglinide does.

To suggest that using repaglinide and glyburide in combination is similar to using two β-blockers is perhaps an oversimplification and misses the essential point of the case report, which is early aggressive pharmaco- logic and nonpharmacologic therapies in combination delay or prevent the dreaded microvascular and macrovas- cular complications of diabetes.

Synergism in medicine is not a new therapeutic concept. It is used in antibiotics and angiotensin II receptor blockers. Why should it not be tried with the different chemical classes of oral hypoglycemic agents to maxi- mize their effect and optimize glycemic control?

We also know that secondary failure among non–insulin-dependent diabetes mellitus patients treated with sulfonylureas is a common problem:

each year 5% of sulfonylurea-treated patients become insensitive to the drug.² Combination therapy using the different properties as well as chemical classes of oral hypoglycemic agents has broad pharmacodynamic appeal, as it allows us ways of improv- ing insulin release, insulin resistance, or both. In a comparative study, repaglinide was shown to be more effective in lowering postprandial glucose levels than the sulfonylurea glyburide.³

The intention of combination therapy is to obtain better glycemic control than can be achieved with either monotherapy or to achieve similar control with reduced doses of individ- ual agents. Combination therapy can also be advantageous if monotherapy is associated with troublesome side effects that reduce compliance.³ Given the lack of specific guidance on the next step for patients with type 2 diabetes who are not adequately controlled using monotherapy, dual therapy, or

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letters

^

correspondance

triple therapy, we need new random- ized controlled trials to assess combination therapy in its current infantile form and for now must reserve judg- ment on what constitutes good clinical practice!

—L.E. Lockman,

MBCHB, MFAMMED(SA), CCFP

References

1. Raskin P, Jovanovic L, Berger S, Schwartz S, Woo V, Ratner R. Repaglinide/troglitazone combination therapy:

improved glycemic control in type 2 diabetes. Diabetes Care 2000;23(7):979-83.

2. Trischitta V, Italia S, Raimondo M, Guardabasso V, Licciardello C, Runello F, et al. Efficacy of combined treat- ments in NIDDM patients with secondary failure to sulpho- nylureas. Is it predictable? J Endocrinol Invest 1998;21:744-7.

3. Moses R. Repaglinide in combination therapy with metformin in type 2 diabetes. Exp Clin Endocrinol Diabetes 1999;107(Suppl 4):S136-9.

Learning the lessons of the HRT fiasco

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s women and their physicians

“jump off the hormone bandwagon,”¹ the next phase of our desire to stay young and defeat the normal course of aging has shifted to male hormone replacement therapy (HRT).

As with ovarian HRT, much of the drive for the use of male hormones comes from crafty campaigns delivered with the backing of the pharmaceutical industry. We have been convinced that there is no reason for men to “slow down” as they age; all we have to do to counteract aging is prescribe HRT for

“androgen-deficient” males. Yes, there will always be patients who desire that eternal ability to perform as they did in their youth (mentally and physi- cally) and who seek our help for this

“problem.”

But the medical profession has the responsibility to learn the lessons of ovarian HRT use. We need to put these requests for help in the context of normal aging and to demonstrate a responsible reluctance to prescribe androgen replacement therapy until there is evidence to support its safe and efficacious long-term use. There are many lessons to be learned from the Women’s Health Initiative; the current trend to prescribe androgen replacement lacks credible evidence of its safety.

—Alan Katz, MD, CCFP, FCFP

Winnipeg, Man by e-mail Reference

1. Cherniak D. Jumping off the hormone bandwagon [letter].

Can Fam Physician 2003;49:422.

Influencing public policy

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n “Diabetes care in Canadian family practice,”¹ Dr Agarwal wrote: “From patients’ perspective, behavioural

change depends on social and eco- nomic priorities.”

In the past 10 years, the prevalence of obesity and overweight has increased among industrialized coun- tries, with adverse effects on type 2 diabetes, hypertension, and serum lip- ids. Our success at convincing people to eat less sugar and fat, to eat less and to exercise more, is low. A reason for this limited success might be the uneven exposure that people have to doctors and other influences.

Multinational companies spend hun- dreds of millions of dollars on advertis- ing each year. Incessant campaigns in the electronic and print media exhort people to drive cars and to eat fatty and sugary foods. Given the fact that people are exposed to these advertis- ing messages far more often than they are to their doctors, it is unsurprising that the prevalence of overweight and obesity has been increasing.

I agree with Dr Agarwal that family doctors have a role in influencing public policy to improve health.

—Robert Shepherd, MD

Gatineau, Que by mail Reference

1. Agarwal G. Diabetes care in Canadian family practice. A newcomer’s perspective [editorial]. Can Fam Physician 2003;49:721-2 (Eng), 728-30 (Fr).

Correction

T

he e-mail address given in the ordering section of the book review of Comfort Care. Palliative Care Symptom Management of Cancer Patients. A Guide for Physicians, 2nd ed (Can Fam Physician 2003;49:791) has changed. The new e-mail address is [email protected].

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1078 Canadian Family Physician • Le Médecin de famille canadien VOL 49: SEPTEMBER • SEPTEMBRE 2003

Weight loss, not drugs.

Letters  Correspondance Letters  Correspondance