1. What does "modified release" mean?
2. Is 1 to 4 tablets of DIAMICRON MR per day really enough?
3. Why is DIAMICRON MR given at breakfast time?
4. Can DIAMICRON MR tablets be divided?
5. Can a once-daily preparation really be suitable for elderly/renal failure patients?
6. Is any sulfonylurea really suitable treatment for obese type 2 diabetic patients?
7. Why a "once-daily" sulfonylurea?
8. Does DIAMICRON MR possess the same hemovascular benefits as DIAMICRON?
9. Should I change my patients treated with DIAMICRON to DIAMICRON MR?

Yes, the total bioavailability (97%) of the new formulation of DIAMICRON MR with the hydrophilic matrix allows optimization of the dosage, with one dose per 30 mg tablet. During the entire development phase, DIAMICRON MR showed an excellent efficacy in all profiles of type 2 diabetic patients in double-blind randomized studies.

DIAMICRON MR, through its innovative hydrophilic matrix formulation, is designed to better match the release of active ingredient to the circadian glycemic levels of type 2 diabetic patients. When given once daily at breakfast, DIAMICRON MR ensures that levels of short-acting active ingredient are highest during the prandial daytime period, and relatively reduced during the fasting nighttime hours. (Figure 1)

Reference:

1. Francillard M, Frey N, Paraire M, Laveille C, Jochemsen R. Pharmacokinetics of Diamicron "Modified Release" (MR) in 1007 Type 2 Diabetic patients. J Nutr Health Aging. 2001;5 (Special issue): 31;14.

No, and in any case it is not necessary, as the results obtained in a pharmacokinetic and pharmacodynamic study in type 2 diabetic patients demonstrated that the dose of 30 mg is the first effective dose of DIAMICRON MR. The clinical efficacy and acceptability of starting DIAMICRON MR at this 1 tablet dose in newly diagnosed or even fragile patients has been demonstrated. The maintenance dose is usually 2 to 4 tablets. This dosage scheme was well demonstrated in the course of large scale clinical studies during the development of the product. Breaking the tablet, and hence the hydrophilic matrix of DIAMICRON MR, could change the unique characteristics of the release profile of the active ingredient (from the tablet as a whole) as well as the absorption of the active ingredient and is therefore not recommended.(Figure 1)

Specific properties of DIAMICRON MR make it particularly suitable for prescription to elderly patients and patients with mild to moderate renal failure. DIAMICRON MR allows better matching of active ingredient levels to the circadian glycemic levels of type 2 diabetic patients. DIAMICRON MR shows freely reversible binding to the ß-cell sulfonylurea receptor, restores the early peak of insulin secretion, and has no active circulating metabolites. The success of this combination of effective and exceptionally well-tolerated sulfonylurea with the innovative formulation of DIAMICRON MR is seen in the results of phase III trials with planned sub-population analyses of elderly patients and those with mild to moderate renal failure. (Figure 1)

Efficacy and acceptability in these fragile populations reflected those in the general study population, effective glycemic control being achieved with a very low incidence of hypoglycemia and avoidance of hypoglycemia at night. Thus DIAMICRON MR has been demonstrated to be a suitable first-line therapy for all type 2 diabetic patients, including the elderly and those with mild to moderate renal failure.

Reference:

1. Crepaldi G, Fioretto P. Gliclazide modified release: its place in the therapeutic armamentarium. Metabolism. 2000;49:21-25.

One of the prime concerns in the treatment of overweight and obese diabetic patients is avoidance of further weight gain. In this context, DIAMICRON MR's demonstrated weight neutrality is an important clinical benefit. A phase III clinical trial confirmed no change in weight during 10 months' DIAMICRON MR treatment of 401 type 2 diabetic patients, even in the obese (BMI>30 kg/m2) patients. (Figure 1)

DIAMICRON MR's formulation better matches release of active ingredient to type 2 diabetic patients' circadian glycemic levels, shows freely reversible interaction with the ß-cell sulfonylurea receptor, restores the early peak of insulin secretion, and has direct effects on insulin sensitivity. These properties of DIAMICRON MR favour prevention of hyperinsulinemia, as confirmed by the stability of fasting insulin levels in clinical trials, and offer an explanation for avoidance of weight gain during DIAMICRON MR therapy.

Reference:

1. Drouin P. DIAMICRON MR study group. DIAMICRON MR once daily is effective and well tolerated in type 2 diabetes. A double-blind, randomised, multinational study. J Diabetes Complications. 2000;14:185-191.

The potential advantages of a once-daily oral antidiabetic preparation in terms of compliance are obvious, particularly in the context of poly-medicated patients.

A comparative study of DIAMICRON MR and glimepiride demonstrated that with an efficacy at least as good, there are 50% fewer hypoglycemia with DIAMICRON MR than with glimepiride.

A strong argument for choosing DIAMICRON MR. There is some evidence that glimepiride is more effective in controlling glycemia if given twice-daily rather than once-daily, ^1,2 and caution is advised in prescribing the latter to elderly patients in an increasing number of countries.³

DIAMICRON MR, with its innovative formulation, allows the release of its active ingredient to match to the circadian glycemic profiles of type 2 diabetic patients. Consequently, DIAMICRON MR offers the combination of proven round-the-clock efficacy (Figure 1) with excellent acceptability, including in the elderly and in patients with mild-to-moderate renal failure.

Reference:

1. Rosenstock J, Samols E, Muchmore DB, et al. Glimepiride, a new once-daily sulfonylurea: a double-blind placebo-controlled study of NIDDM patients. Diabetes Care. 1996;19:1194-1199.
2. Langtry HD, Balfour JA. Glimepiride: a review of its use in the management of type 2 diabetes mellitus. Drugs. 1998;55:563-584.
3. Summary of product characteristics for glipizide. GITS: France, Turkey, USA.
4. Guillausseau PJ, Greb W. 24-hour glycemic profile in type 2 diabetic patients treated with gliclazide modified release once daily. Diabete Metabol. 2001;27:133-137.

Yes, DIAMICRON MR possesses the same hemovascular benefits as DIAMICRON 80mg. Phase III development demonstrated that DIAMICRON MR, once daily, significantly and persistently decreased several markers of oxidative stress and lipid oxidation in type 2 diabetic patients. (Figure 1)

Several studies have shown that, because of its aminoazabicyclo[3.3.0]octane ring, the active ingredient possesses specific benefits independent of effective blood glucose control, for example:

1. Inhibition of two key steps in the formation of atheroma:
   
   1. by reduction of lipid peroxidation;
      
   2. by reduction of adhesivity of monocytes to the vascular endothelium.
      
      
2. DIAMICRON MR counteracts the formation of thrombus by reducing platelet hyperactivity and aggregation.
   The long-term efficacy of metabolic control and the unique hemovascular properties of DIAMICRON MR satisfy the main objective of treatment of type 2 diabetes mellitus: reduction of vascular complications.

Reference:

1. O'Brien RC, Luo M, Balazs N, Mercuri J. In vitro and in vivo antioxidant properties of gliclazide. J Diabetes Complications. 2000;14:201-206.

In the treatment of type 2 diabetes, the key factor to success is the efficacy of long-term metabolic control. Thanks to a once-daily dose taken at breakfast, DIAMICRON MR makes it possible to improve patient compliance, a key factor in obtaining this level of metabolic control. In addition, the new hydrophilic matrix of DIAMICRON MR, offers essential pharmacokinetic advantages:

release of the right dose of active ingredient at the right time: plasma concentrations are higher during the prandial period of the day, allowing effective 24-hours blood glucose control with a very low incidence of hypoglycemia and no nocturnal hypoglycemic episodes;

total absorption, allowing optimization of the 80 mg dose at 30 mg of active ingredient per tablet;

absorption unaffected by ingestion of food;

reliable release and reproducible control day after day.

The DINAMIC 2¹ study proofs that DIAMICRON MR is more effective and more practical than DIAMICRON 80mg with patients taking their tablets only at breakfast, without compromising safety and obtaining 100 % compliance. This proof has been very recently reinforced by a study in which 2160 patients were switched from DIAMICRON 80 to DIAMICRON MR, and who benefited from a significant improvement of their blood glucose control of 0.6% HbA_1c.²

If you want your patients to benefit from these added clinical benefits, it is wise to change patients to DIAMICRON MR on a tablet for tablet basis.

Reference:

1. Sieradzki J. Application of gliclazide MR in uncontrolled diabetes type 2. The treatment phase results of DINAMIC 2 study. Diabetologia Praktyczna. 2003;4:133-136.
2. Guillausseau PJ. Compliance and optimization of oral antidiabetic therapy. A longitudinal study. Presse Med. 2004;33:156-160.