Gliclazide: Endurance and evolution with the demands and standards of diabetes care

Diabetes mellitus continues to exert immense burden, affecting individuals, families, and countries. Sadly, scientific projections show that this burden will continue to grow significantly.¹ In response to this predicament, scientific medical communities tirelessly seek new knowledge and solutions to keep pace with the evolving needs of diabetes patients. Updates in local and international guidelines have put emphasis on a comprehensive approach especially in pharmacologic management with renewed focus on comorbidities, patient-centered treatment factors and management needs.   

Gliclazide and the other sulfonylureas^2,3  
Sulfonylureas (SUs) were the first oral hypoglycemic agents to be developed for the treatment of type 2 diabetes mellitus in the 1950s. To date, it remains to be the most widely prescribed oral hypoglycemic agent worldwide, together with metformin, and still the most common choice for second-line therapy.   Various concerns on the side- effects of SUs, mainly regarding hypoglycemia, weight gain and cardiovascular risk, have limited their clinical use. Since their introduction into the market however, the SUs have undergone several stages of development and emerging evidence show that side effects are not a class characteristic and that the drugs in this class have different pharmacologic properties.  

Recent clinical trials have established that the true risk for severe hypoglycemia with SUs is low, in contrast to reports from observational studies. This is especially true with later-generation agents like gliclazide. No increased risk of mortality or morbidity from CVD has been shown in recent studies, with gliclazide associated with the lowest risks. No significant weight gain associated with the use of SU was reported in the ADVANCE study. Other studies showed weight gain was either temporary or happened only during the initial phase of treatment with body weight stabilizing or returning to baseline for the rest of the treatment course.   

Recent studies have also shown that third-generation SUs like gliclazide MR possess many of the clinical qualities of an ideal medication for type 2 diabetes including efficacious glycemic control, convenient once-a-day oral administration, fewer and milder side effects, cardiovascular safety and cost-effectiveness.  This has helped gliclazide to sustain its presence in various clinical practice guidelines.  

Sulfonylureas in the Local Guidelines on the Management of Diabetes Mellitus⁴
The Philippine clinical practice guidelines for the management of diabetes mellitus combines the best external evidence and local clinical experience to come up with evidence-based and cost-effective recommendations that are adapted to the local setting and incorporates patients’ decision-making values and issues of equity. It recognizes SUs as a second-line drug for optimization of therapy, making note of its efficacy in lowering HbA1c by 1-2%. Together with metformin, it holds the highest efficacy rating among the oral hypoglycemic agents recommended by the guideline.  

The use of a second-line drug - a combination therapy with metformin – is recommended in cases of higher blood sugar levels (FBS ≥250mg/dL or HbA1c of ≥9%), in symptomatic patients or in those where monotherapy has failed to achieve glycemic control.    

Sulfonylureas in international guidelines³  
Despite differences in guideline recommendations, SUs have maintained its status as a second-line drug in several international guidelines. Based on the AGREE II guideline developed by the International Diabetes Foundation to rate the quality of clinical guidelines, SUs were recommended by the highest-ranked NICE guideline as first-choice add-on therapy. Other guidelines also included SUs with some making specifications for gliclazide.



Through the years, SUs have remained to be the dependable, efficacious, safe and cost-effective oral hypoglycemic agents that continue to be recommended by local and international guidelines for the pharmacologic management of type 2 diabetes mellitus. Gliclazide has been shown to have the most beneficial impact especially on cardiovascular risk and severe hypoglycemia. And as new knowledge about diabetes and its management continue to accumulate, better understanding and deeper insights into SUs and other oral hypoglycemic agents could only propel the health-related quality of life of people living with diabetes to new heights.