perspectivas terapéuticas para la Diabetes Mellitus
1: Drugs 2002;62(9):1357-64;
Gliclazide modified release.
McGavin JK, Perry CM, Goa KL.
Adis International Limited, Auckland, New
Gliclazide modified release (MR) is a new
formulation of the drug gliclazide and is given once daily. The
hydrophilic matrix of hypromellose-based polymer in the new formulation
effects a progressive release of the drug which parallels the 24-hour
glycaemic profile in untreated patients with type 2 diabetes mellitus. The
formulation shows high bioavailability and its absorption profile is
unaffected by coadministration with food. Mean plasma glucose levels are
significantly reduced over a 24-hour period in patients with type 2
diabetes mellitus treated with gliclazide MR once daily, in both fasting
and postprandial states. No cardiovascular ATP-sensitive potassium channel
interaction has been observed at therapeutic concentrations of gliclazide
MR. Gliclazide MR has also demonstrated antioxidant properties that are
independent of glycaemic control. In a randomised, double-blind,
multicentre study, gliclazide MR 30 to 120 mg once daily showed similar
efficacy to gliclazide immediate release (IR) 80 to 320 mg/day (in divided
doses for doses >80 mg) in patients with type 2 diabetes mellitus over
a 10-month period, reducing glycosylated haemoglobin (HbA(1c)) and fasting
plasma glucose (FPG) to a similar extent. The drug appeared most
efficacious in patients who had previously been treated by diet alone,
where significant reductions in HbA(1c) from baseline of 0.9% and 0.95%
were seen at 10 and 24 months. Similarly, a sustained effect of gliclazide
MR was observed in a subgroup of elderly patients defined a priori; HbA(1c)
was decreased to a similar degree to that observed in the general study
population. Gliclazide MR showed similar tolerability to gliclazide IR
after 10 months' treatment in the randomised trial. The most commonly
observed adverse events were arthralgia, arthritis, back pain and
bronchitis (each <5%). Bodyweight remained stable. In this study no
episodes of nocturnal hypoglycaemia or hypoglycaemia requiring third party
assistance were observed during treatment with gliclazide MR. Episodes of
symptomatic hypoglycaemia were infrequent, occurring in approximately 5%
2: Diabetes Care 2002 Feb;25(2):390-4
Treatment issues in type 2 diabetes.
Diabetes Center, Mount Sinai School of Medicine,
New York, NY, USA.
3: Lancet 2001
Insulinotropic meglitinide analogues.
Department of Metabolic Medicine, Faculty of
Medicine, Imperial College, Hammersmith Hospital Campus, Du Cane Road, W12
0NN, London, UK. firstname.lastname@example.org
The loss of early-phase insulin secretion is an
important and early event in the natural history of type 2 diabetes.
Because a normal pattern of insulin secretion is essential for the
effective control of postprandial metabolism, a rational basis for the
development of agents that target early-phase insulin release exists.
Conventional oral hypoglycaemic agents do not target, or adequately
control, postprandial glycaemia. The emergence of new classes of oral
agent with a more specific mode of action provides, for the first time, an
opportunity to restore early-phase insulin release. One such drug class is
the meglitinide analogues (repaglinide, nateglinide, and mitiglinide).
These drugs are ideally suited for combination use with metformin. They
could also prove effective in combination with a thiazolidinedione, a drug
class that targets insulin resistance. Exogenous insulin is frequently
required in the late management of type 2 diabetes. However, one hope for
newer combinations of diabetic drugs is that the functional life of the
beta cell can be extended, thereby delaying the need for insulin
4: Endocrinol Metab Clin North Am
Oral therapies for diabetic hyperglycemia.
Department of Medicine, State University of New
York Health Science Center at Brooklyn, Brooklyn, New York, USA.
Many classes of oral antihyperglycemic agents
are available for the treatment of type 2 diabetic patients. These classes
improve glucose metabolism by different mechanisms, and their effects are
additive. Therapy with lifestyle modification and a single oral
antihyperglycemic agent infrequently achieves target glycemic goals, and,
if it does, the effect is usually not sustained. A more rational approach
would seem to be therapy with combinations of drugs with different
mechanisms of action. Initial therapy might be with submaximal
concentrations of two drugs. As the diabetic abnormalities progress,
maximal concentrations of the drugs and addition of other classes of oral
agents or insulin may be needed to maintain the target glycemic goal. In
choosing combinations of oral antihyperglycemic agents, their effects on
the components treatment of type 2 diabetic patients. These classes
improve glucose considered, as must the specific effects of the agents on
5: Hosp Pract (Off Ed)
2001 Sep 15;36(9):29-36 [Texto
Type 2 diabetes: new drugs, new perspectives.
Joslin Diabetes Center, Boston, USA.
Detection at younger ages is rapidly increasing.
Although diet and exercise remain the mainstays of therapy, physicians can
now choose from among a variety of medications targeting different
pathophysiologic facets of the disease. The newest drugs are the
thiazolidinediones, a totally novel class of insulin sensitizers.
6: An Med Interna 2001 Jul;18(7):381-8
Objectives and therapeutic strategy in type 2
Calvo Romero JM, Lima Rodriguez EM.
Servicio de Medicina Interna, Hospital Regional
Universitario Infanta Cristina, Badajoz.
United Kingdom Prospective Diabetes Study (UKPDS)
has demonstrated definitively that patients with type 2 diabetes mellitus
(DM) benefit from intensive blood glucose control, because it diminishes
the risk to develop microvascular complications. The therapeutic targets
in the type 2 DM have been modified in order to reduce the risk of these
complications. However, aggressive treatment may be disastrous for
patients with microvascular complications and/or an increased risk of
hypoglycemic unawareness, and neither it would be advised in older
patients or with short life expectancy. The available drugs for treatment
of type 2 DM offer many options for achieving these therapeutic targets,
based on the need of the individual patient. In this job we review the
targets in the metabolic control of type 2 DM and their backgrounds, and
we describe briefly the therapeutic strategy recommended for reaching
these targets, with special attention to the new oral antidiabetic agents
(repaglinide and thiazolidinediones).
7: Am Fam Physician 2001 May 1;63(9):1687-8, 1691-2, 1694
Treatment of type 2 diabetes mellitus: a
rational approach based on its pathophysiology.
Reasner CA, Defronzo RA.
8: Diabetes Metab 2001 Apr;27(2 Pt 2):287-93
Type 2 diabetes mellitus: Which place for
thiazolidinediones in the therapeutic strategy?
Service Endocrinologie, Diabetologie, Nutrition
CHU de Grenoble, Grenoble, France. email@example.com
Several new pharmacological agents have recently
been developed to optimise the management of type 2 diabetes mellitus. The
aim of this article is to briefly review the new therapeutic class:
thiazolidinediones (TZD), acting as these insulin sensitizer and to
suggest a logical use of these drugs in the guidelines proposed by the
french recommendations for the treatment of type 2 diabetic subjects.
These agents are now introduced in Europe, only in combination with
metformin or sulfonylureas (or glinides). Moreover, some preliminary data
indicate that these agents could delay the decrease of insulin secretion
by the beta pancreatic cells and could reduce other cardiovascular risk
factors often associated with type 2 diabetes: hypertension and lipid
abnormalities, by reducing blood pressure, triglycerides and increasing
HDL cholesterol. These new drugs bring some hope in the treatment of type
2 diabetic patients in combination with the previous oral anti-diabetic
drugs which have recently demonstrated (UKPDS) their ability to prevent or
to reduce complications due to diabetes. However the frequency of adverse
events must be evaluated in a large use, beyond phase II and III, after
the withdrawal of the first TZD introduced on the market (troglitazone).
2001 Jun;56(6):20-4, 32-3
Type 2 diabetes. How new insights, new drugs
are changing clinical practice.
Drexler AJ, Robertson C.
Mount Sinai School of Medicine, Diabetes Center,
Mount Sinai Medical Center, New York, NY, USA.
In 1997, the American Diabetes Association
recommended a normal fasting blood glucose of < 126 mg/dL as the
criteria for diagnosis of type 2 diabetes. Since then, new data have
suggested that post-prandial glucose may have a stronger correlation with
cardiovascular disease than fasting blood glucose. Two trials, the DCCT
and UKPDS, provided evidence of the relationship between hyperglycemia and
long-term diabetic complications. Preventing short-term complications,
such as cognitive decline, is a more immediate goal and less well-studied.
Type 2 diabetes is understood to result most often from insulin resistance
and insulin deficiency. New classes of drugs offer expanded therapeutic
options for managing this dual metabolic defect. These drugs have
invalidated the former therapeutic paradigm of diet, sulfonylureas, and
then insulin therapy.
10: Rev Esp Cardiol 2001 Jun;54(6):751-63 [Texto
Diabetes mellitus, inflammation and coronary
atherosclerosis: current and future perspectives
Sanchez-Recalde A, Carlos Kaski J.
Coronary Artery Disease Research Unit,
Department of Cardiological Sciences, St. George's Hospital Medical School,
Type 2 diabetes mellitus is a condition
associated with an increased risk of coronary artery disease. This
condition is currently reaching epidemic proportions in the Western world.
Epidemiological studies have shown that insulin resistance and the
constellation of metabolic alterations associated with type 2 diabetes
mellitus such as dyslipidaemia, systemic hypertension, obesity and
hypercoagulability, have an effect on the premature onset and severity of
atherosclerosis. Albeit direct, the link between insulin resistance and
atherogenesis is rather complex. It is likely that its complexity relates
to the interaction between genes that predispose to insulin resistance and
genes that independently regulate lipid metabolism, coagulation processes
and biological responses of the arterial wall. The rapid development of
molecular biology in recent years has resulted in a better understanding
of the immune and inflammatory mechanisms that underlie insulin resistance
and atherosclerosis. For example, it is known that nuclear transcription
factors such as nuclear factor kappa beta and peroxisome proliferator-activated
receptor are involved in atherosclerosis. The former modulates gene
expression which encodes pro-inflammatory proteins vital for the
development of the atheromatous plaque. In the presence of insulin
resistance there are multiple activating factors that could explain the
early onset and severity of atherosclerosis. Glitazones, the new oral
antidiabetic drugs and agonists of peroxisome proliferator-activated
receptor, have been shown to improve peripheral insulin sensitivity and to
also delay atherosclerosis progression in experimental models. Their
beneficial effects have been linked to their anti-inflammatory effect.
11: Drugs Aging 2000 Nov;17(5):411-25
Meglitinide analogues in the treatment of
type 2 diabetes mellitus.
Diabetes Center, Department of Internal
Medicine, University of Munich, Germany. firstname.lastname@example.org
Type 2 diabetes mellitus is a complex
heterogenous metabolic disorder in which peripheral insulin resistance and
impaired insulin release are the main pathogenetic factors. The rapid
response of the pancreatic beta-cells to glucose is already markedly
disturbed in the early stages of type 2 diabetes mellitus. The consequence
is often postprandial hyperglycaemia, which seems to be extremely
important in the development of secondary complications, especially
macrovascular disease. Therefore one of the main aims of treatment is to
minimise bood glucose oscillations and attain near-normal glycosylated
haemoglobin levels. Meglitinide analogues belong to a new family of
insulin secretagogues which stimulate insulin release by inhibiting ATP-sensitive
potassium channels of the beta-cell membrane via binding to a receptor
distinct from that of sulphonylureas (SUR1/KIR 6.2). The pharmacokinetic
and pharmacodynamic properties of repaglinide, the first drug of these new
antihyperglycaemic agents on the market, and of nateglinide, which will be
available soon, differ markedly from the currently used sulphonylureas [mainly
glibenclamide (glyburide) and glimepiride]. Repaglinide and nateglinide
are absorbed rapidly, stimulate insulin release within a few minutes, are
rapidly metabolised in the liver and are mainly excreted in the bile.
Therefore, following preprandial administration of these drugs, insulin is
more readily available during and just after the meal. This leads to a
significant reduction in postprandial hyperglycaemia without the danger of
hypoglycaemia between meals. The short action of these compounds and
biliary elimination makes repaglinide and nateglinide especially suitable
for patients with type 2 diabetes mellitus who would like to have a more
flexible lifestyle, need more flexibility because of unplanned eating
behaviour (e.g. geriatric patients) or in whom one of the other first-line
antidiabetic drugs, i.e. metformin, is strictly contraindicated (e.g.
nephropathy with creatinine clearance < or = 50 ml/min). Meglitinide
analogues act synergistically with metformin and thiazolidinediones (pioglitazone
and rosiglitazone) and can be also combined with long-acting insulin (NPH
insulin at bedtime). Therefore, these drugs enrich the palette of
antidiabetic drugs and make the treatment more flexible and better
tolerated, which both add to better metabolic control and support the
empowerment and compliance of the patient. However, this will only be the
case if the patient and the diabetes care team are trained for this new
therapeutic schedule and the healthcare system is able to pay for these
rather expensive drugs.
12: Manag Care
2000 Aug;9(8 Suppl):11-7; discussion 24-8
Management of type 2 diabetes: update on new
Department of Medicine, Ochsner Clinic, New
The value of intensive control of blood glucose
levels has been clearly established. Data from the UKPDS demonstrated that
improving glycemic control will reduce the risk of microvascular
complications of type 2 diabetes, such as diabetic retinopathy,
nephropathy, and peripheral neuropathy. Further, the metformin study in
overweight patients and the epidemiological analysis of the study both
demonstrated a reduction in macrovascular complications and mortality
related to improved glycemic control. These findings should enhance
awareness among both patients and physicians of the dangers of
uncontrolled hyperglycemia and the need for early diagnosis and aggressive
treatment for patients with type 2 diabetes. Optimal management of type 2
diabetes most often requires a combination of glucose-lowering medications
to achieve glycemic control. Current guidelines for combination therapy
advise the use of agents with differing and complementary mechanisms of
action in order to maximize therapeutic activity and reduce toxicity.
Earlier introduction of combination therapy is increasingly being
recommended. The new glyburide/metformin combination medication may
facilitate earlier, more appropriate and more effective treatment for
patients with type 2 diabetes.
13: Diabetes Care 1999 Jul;22(7):1209-15
The European Association for the Study of
Diabetes Annual Meeting, 1998. Treatment of type 2 diabetes and the
pathogenesis of complications.
Division of Endocrinology, Mount Sinai School of
Medicine, New York, New York, USA.