LETTERSpathy at baseline was more advanced in before starting these studies the protocolsReferencesthe group of patients who were later were separately approved by the ethical

committee of each institution.switched to insulin treatment than in the1. Henricsson M, Nilsson A, Janzon L,group who continued with oral agents or The objectives of the studies were

Groop L. The effect of glycemicdiet alone throughout the study.’ Finally different. The purpose of the study incontrol and the introduction of insu-the authors state, ‘Neither insulin treat- patients previously treated by diet was tolin therapy on retinopathy in non-ment per se nor antihypertensive treatment investigate a hypoglycaemic effect andinsulin-dependent diabetes mellitus.were independent risk factors for retino- whether hypoglycaemic episodesDiabetic Med 1997; 14: 123–131.pathy progression in the multivariate occurred when troglitazone was used as

2. The DCCT Research Group. Theanalysis.’ monotherapy. On the other hand theeffect of intensive treatment of dia-Comparing the oral agent to insulin objective of the high dose SU study wasbetes on the development and pro-group in this study with the better con- to investigate the clinical usefulness ofgression of long-term complicationstrolled insulin or oral agent groups did this drug as a combination therapy. Thein insulin-dependent diabetes mel-not offer a fair comparison. The former patients in this study were sulphonylurealitus. N Engl J Med 1993; 329:group had the poorest metabolic control failures. In Japan, the recommended daily977–986.and were thus at greatest risk of developing dose of glibenclamide is 1.25 mg to 10 mg

3. Ohkubo Y, Kishikawa H, Araki E, etretinopathy. The extended period of poor and that of gliclazide is 20 mg to 160 mg.al. Intensive insulin therapy preventscontrol had already resulted in a higher The inclusion criteria for this study were:the progression of diabetic microvas-prevalence of retinopathy at baseline. ‘higher than 5 mg glibenclamide or highercular complications in JapaneseHence a ‘controlled’ study with this group than 80 mg of gliclazide’ so we concludedpatients with non-insulin dependentof patients would have randomized a that these patients were not controlleddiabetes mellitus: a randomized pro-portion of the patients to improved control satisfactorily by high dose sulphonylureas.spective 6-year study. Diabeteswith insulin while others maintained poor Patients who fail to respond to suchResearch and Clinical Practice 1995:control on oral agents. treatment are routinely placed on exogen-28; 103–117.Several other conclusions may be ous insulin therapy.

drawn from this data. First, Henricsson’s In previous clinical studies hypoglyca-emic episodes has only been observedstudy only strengthens the evidence that

early and aggressive treatment with insulin with combination of sulphonylurea andtroglitazone. In the troglitazone monother-or oral agents may reduce incidence and

progression of diabetic complications. apy studies there were no hypoglycaemicsymptoms for both patients with Type 2Allowing blood glucose values to be out A Miracle of Salamization: Positive Div-

of control for extended periods of time diabetes and also for healthy subjects.ided by Two Equals Negativewhile on oral agents is associated with a We intended to carry out two separate

studies and so we wrote two separateworse outcome.On behalf of the authors and participatingSecond, this study confirms that the articles. We agree that it may have beenscientists in the troglitazone clinical stud-progression of retinopathy, as well as easier for readers or others to understandies in Japan, I would like to express ourother complications of diabetes, is associa- our findings if these two articles hadopinions on the letter in your journal: Ated with the degree of glycaemic control. been submitted simultaneously to themiracle of salamization: positive dividedPatients with the poorest metabolic con- same journal.by two equals negative.1trol in Henricsson’s study were those Thank you for your comments.

During the same period we carried outchanged from oral agent to insulin ther-two different double blind clinical studiesapy. The average HbAlc in oral agent to Y. Iwamotoin Japan using troglitazone and matchinginsulin group (8.9 ± 1.4 %) was statisti- Diabetes Centre, Tokyo Women’s Medicalplacebo. In these studies there werecally higher than the insulin therapy College, Tokyo, Japandifferences in the populations studied: ingroup (7.8 ± 2.4 %) and the oral agentthe first study the subjects were Type 2group (6.9 ± 1.3 %).diabetes patients previously treated byIn conclusion, optimal metabolic con-diet alone2 and in the second study thetrol is the most effective means of improv-subjects were Type 2 diabetes patientsing the risk for development and pro- Referencespreviously treated with high dose sulphon-gression of the chronic complications ofylureas.3 These two treatment populationsdiabetes, particularly retinopathy. Insulincan be said to represent the extremes of 1. Gurlek A, Ozdemir O. A miracle oftherapy, when initiated at an appropriatelythe diabetes spectrum: diet treatment salamization: positive divided byearly point in the disease, is effective inalone suggesting that these patients are two equals negative. Diabetic Medcontrolling blood glucose and should,at an earlier stage of their disease than 1997; 14: 334–335.therefore, reduce the risk of progression ofpatients treated with high dose sulphonyl- 2. Iwamoto Y, Kosaka K, Kuzuya T,complications in diabetes. Insulin remainsureas. Akanuma Y, Shigeta Y, Kaneko T.the only glucose lowering agent demon-

Although these two protocols were Effects of troglitazone: a new hypog-strated in long-term clinical trials2,3 todesigned at the same time, the test drugs, lycemic agent in patients withreduce the risk of development and pro-the manuals for getting informed consent, NIDDM poorly controlled by dietgression of the chronic complications ofthe case report forms and the studies therapy. Diabetes Care 1996; 19:Type 1 and Type 2 diabetes.themselves were carried out at different 151–156.

3. Iwamoto Y, Kosaka K, Kuzuya T,institutes. Some institutes carried out onlyone protocol and others both protocols.E.J. Bastyr III,1 J. Janes,2 A.H. Barnett3 Akanuma Y, Shigeta Y, Kaneko T.

Effects of combination therapy of1Lilly Research Laboratories, Eli Lilly and Seventy-six study centres participated inthe monotherapy study and 59 centresCompany, Lilly Corporate Center, Indian- troglitazone and sulphonylurea in

patients with Type 2 diabetes whoapolis, Indiana, USA participated in the combination study.The study period was longer in the2Lilly, Basingstoke, UK were poorly controlled by sulphonyl-

urea therapy alone. Diabetic Med3Department of Medicine, University of monotherapy study (14 months) than thecombination study (12 months). Certainly,Birmingham, Birmingham, UK 1996; 13: 365–370.

994 LETTERS

Diabet. Med. 14: 989–994 (1997) 1997 by John Wiley & Sons, Ltd.