INSULIN GLARGINE COMBINED WITH ORAL AGENT IN T2DM (CLINICAL USES OF FORMULAS: 1/3, 5-5, 2-2, 1-1, AND 1-2)
ABSTRACT: A map of oral agents
for diabetes (OADS), either at present or in the future should be well
recognized. Four of such OADS (glimepiride, glinides, gliclazide, metformin)
have claimed showing atheroprotective
properties beyond its hypoglycemic or anti- hypoglycemic effects. On the basis
of clinical experiences and molecular mechanisms, glimepiride (GLIM) can be
summarized having 3B - 3A - 9D properties: 3-fold higher rate of Binding to
receptor (3B), 3-fold lower Affinity to receptor (3A), and 9-fold faster rate
of Dissociation from receptor (9D). These effects (3B-3A-9D) may result in
potential therapeutical benefits, including: rapid onset (due to 3-fold higher
rate of Binding = 3B) and less hypoglycemic events due to lower Affinity (3A)
and faster Dissociation (9D). By using therapeutic concentration (in contrast
to glibenclamide), GLIM (via PI3-Kinase Pathway) increases insulin - stimulated
glycogen synthesis (GS) in human muscle cells (GS effect). In addition, GLIM
inhibits platelet aggregation which may in turn have a preventive effect on the
development of diabetic vascular
complications (more pronounced effect than gliclazide). The ideal basal insulin should ideally have
the following six characteristics: 1. mimics normal pancreatic basal insulin
secretion, 2. long-lasting 24-hour effect, 3. smooth, peakless profile, 4.
reproducible and predictable effects, 5. reduces risk of nocturnal hypoglycemia, and 6. once-daily administration. Insulin
Glargine (GLAR) is a novel peakless long-acting insulin analogue that is
available for clinical use and it has a smooth profile and long, 24-hour
duration of action. Thus, GLAR is an improved basal component for combination
regimens (Method A, B, and C) with OADS in the treatment of type 2 diabetes
mellitus (T2DM). The most frequent indication of CTOI is, patients with T2DM
who failed to be treated with a maximal dose of OHA, although medical nutrition
therapy (MNT) and programmed regular exercise have been perfectly adhered to.
Based on clinical experiences another 6 (six) indications of CTOI are listed in
this manuscript. For the clinical practice point of view, Formulas: 1/3, 5-5,
2-2, 1-1 and Formula 1-2 are provided for the CTOI in the management of
patients with T2DM. GLIM can be combined with insulin therapy (f.e. with GLAR)
in the treatment of T2DM. Based on the clinical experiences, such a combination
can be performed by 3 Methods such as Method- A : both GLIM-GLAR administered
in the Morning, Method- B : GLAR-Morning and GLIM-Evening, and Method- C :
GLIM-Morning and GLAR-Evening. Conclusions: GLIM is 3 gen. sulphonylurea which
shows quintuple pleiotropic cardioprotective properties beyond its hypoglycemic
effect. GLAR is a human peakless insulin analogue that exhibits a 24-hours
action profile (as a basal insulin) with fewer episodes of nocturnal hypoglycemia.
Thus, the CTOI: GLIM and GLAR
combination, may provide for
cardioprotective properties. On the basis of clinical experiences,
Method-A (by using a prebreakfast injection of insulin GLAR coincides with
GLIM) has been proven to be most effective and well tolerated. Abbreviations:
OADS = oral agents for diabetes; GLIM = glimepiride; GLAR = insulin glargine; B
= binding; A = affinity; D = dissociation; GS = glycogen synthesis; CTOI =
combined therapy OAD with insulin; T2DM = type 2 diabetes mellitus; T1DM = type
1 diabetes mellitus; MNT = medical nutrition therapy; GP = general
practitioner.
Author: Askandar Tjokroprawiro
Journal Code: jpkedokterangg050023

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