Quick-release (QR) bromocriptine is a well tolerated and effective therapy for Type 2 diabetes and is not associated with increased cardiovascular (CV) risk, report researchers.

Bromocriptine, a D2 dopamine receptor agonist, is used to treat conditions such as pituitary tumors and Parkinson’s disease. It has recently been shown to significantly reduce glycated hemoglobin (HbA1c) levels by around 0.5% and is now indicated for treatment of patients with Type 2 diabetes.

However, previous studies have been underpowered to assess cardiovascular safety of the drug. To test the overall safety and tolerability of bromocriptine for treatment of Type 2 diabetes, J Michael Gaziano (Harvard Medical School, Boston, Massachusetts, USA) and colleagues randomly assigned 3095 patients with Type 2 diabetes in a 2:1 fashion to take QR bromocriptine (titrated to a maximum of 4.8 mg/day) or placebo, both in addition to their usual diabetes therapy, for a period of 52 weeks.

All adverse events were assessed, with a particular focus on CV disease events - including a combined endpoint of myocardial infarction, stroke, coronary revascularization, and hospitalization for angina or congestive heart failure.

As reported in the journal Diabetes Care, 89% of the bromocriptine group and 83% of the placebo group reported some form of adverse events. In addition, 176 (8.6%) people in the bromocriptine group reported serious adverse events and 98 (9.6%) in the placebo group.

The combined CV disease endpoint was reported by 37 (1.8%) of the bromocriptine group compared with 32 (3.2%) of the placebo group.

The most commonly reported bromocriptine associated adverse event was nausea, reported in 7.6% of the bromocriptine treated patients compared with only 1.0% of the placebo group.

“Nausea was the chief limiting adverse event in this trial. For the majority of patients experiencing nausea, the symptoms occurred during the initial titration of the drug and lasted less than 2 weeks,” write the authors.

“Bromocriptine-QR represents a new treatment modality for Type 2 diabetes,” conclude Gaziono et al. “This first-in-class therapy may provide a new approach to addressing the comorbidities associated with Type 2 diabetes.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Free abstract

New results from a post-hoc analysis of the
BARI-2D trial show no association between rosiglitazone and
cardiovascular (CV) events.

However, the results confirmed previously reported links between
rosiglitazone and fracture.

Richard Bach (Washington University School of Medicine, St
Louis, Missouri, USA) presented the results of a post-hoc study of
2368 patients enrolled in the BARI-2D (Bypass Angioplasty
Revascularization Investigation 2 Diabetes) study at the American
Diabetes Association 2010 Scientific Sessions held in Orlando,
Florida.

The patients all had Type 2 diabetes and
angiographically-confirmed coronary artery disease (CAD) plus at
least one significant lesion suitable for revascularization. The
trial aimed to assess the long-term outcomes of rosiglitazone
therapy.

The main results of BARI-2D have already been published.
Patients were randomized to treatment with prompt revascularization
and medical therapy versus medical therapy and delayed or no
revascularization, and to insulin sensitization versus insulin
provision. The findings showed that the rate of overall survival
and freedom from CV events did not vary significantly between the
different treatment groups, as previously reported by MedWire
News.

For the purposes of this study, Bach and team compared 992
patients treated with rosiglitazone with 1199 patients who were not
treated with a thiazolidinedione (TZD).

At baseline, the patients were aged 62 years on average, had a
mean glycated hemoglobin level of between 7.5% and 7.8%, and had
had diabetes for approximately 10 years. In addition, a quarter of
patients in both groups had undergone prior revascularization.

Bach reported that, at 4.5 years, patients taking rosiglitazone
had a significantly lower rate of stroke and the combination of
death, myocardial infarction (MI), and stroke per 100 patient years
compared with patients not treated with TZDs. In addition, the rate
of death and MI were non-significantly lower, and chronic heart
failure was non-significantly higher in rosiglitazone-treated
patients.

Co-administration with insulin, metformin, nitrates, and
angiotensin-converting enzyme inhibitors, did not significantly
influence the rate of CV outcomes in rosiglitazone treated
patients.

Notably, as found in previous studies, the relative risk for
fracture was a significant 62% higher in rosiglitazone-treated
patients than in those who took no TZDs. When stratified by gender,
the increase in relative risk was statistically significant in
women only, at 82%.

Bach acknowledged that the study was limited by its
non-randomized nature and added that the fact that many patients on
the study were taking more than one anti-diabetic drug might have
limited the ability of the researchers to discriminate the effects
of any one drug from another.

“I think these data are important because they suggest there is
no significant cardiovascular harm posed by taking rosiglitazone
for patients with Type 2 diabetes and coronary heart disease,” said
Bach.

These new data “contribute to the scientific inquiry regarding
associated events with rosiglitazone.”

He added: ” There is an increase in fractures, but when one
considers the dramatic morbidity and mortality associated with
ischemic cardiovascular events in patients with diabetes, these
data are reassuring.”

MedWire (www.medwire-news.md) is an independent clinical news
service provided by Current Medicine Group, a trading division of
Springer Healthcare Limited. © Springer Healthcare Ltd;
2010

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Revascularization no better than medical therapy for stable IHD in Type 2 diabetics

IMPERCEPTIBLE DOES NOT MEAN HARMLESS

The perceptible type 2 diabetes symptoms are frequently absent, soft or intermittent, causing this disease to go unnoticed, sometimes for years. Nevertheless, serious long-term complications will result from these imperceptible type 2 diabetes symptoms anyway. These complications include vascular disease, coronary artery disease, renal failure due to nephropathy, vision problems due to retinopathy, tingling or loss of sensation, burning feet or feet pain due to neuropathy, heart failure from cardiomyopathy, and liver damage from steatohepatitis, among others.

Type?2 diabetes is habitually treated at the start by just escalating corporal activity and diminishing carbohydrate intake and body weight. These can bring back insulin sensitivity even when the mass loss is modest, for instance around 10 or 15?lb, particularly when it is in abdominal overweight.

It is frequently possible to attain long-term acceptable blood glucose control and lessen the diabetes symptoms with these measures alone. However, the core tendency to insulin resistance is not gone, and so consideration to diet, weight loss and exercise must persist. The customary next step, if required, is treatment with oral antidiabetic medication.

TAKE CONTROL: DO NOT PROCRASTINATE

When the ailment progresses, the inability of insulin secretion worsens too, and therapeutic substitution of insulin frequently becomes indispensable. There are abundant theories as to the precise mechanism in type?2 diabetes and its origin.

Fat located around the waist in relation to abdominal organs, called central obesity, is known to incline individuals to insulin resistance. Abdominal fat is especially vigorous hormonally, secreting a set of hormones called adipokines that may probably damage glucose tolerance.

Obesity is present in more than 50% of patients diagnosed with type?2 diabetes. Other possible causes include aging and family history: almost 20 percent of aged patients in the USA suffer from diabetes, and type?2 is much more widespread in those with relatives who have had it.

Type?2 diabetes has begun to affect more and more children and adolescents in the last 10 years, probably in association with the increased occurrence of childhood obesity seen in some places in recent decades.

Low levels of blood sugar, called hypoglycemia, one of the most dangerous symptoms of diabetes, may lead to seizures or episodes of coma and must be treated immediately, via an emergency high-glucose gel positioned in the patient’s oral cavity, or an injection of glucagon or intravenous dextrose.

Type?2 diabetes mellitus is due to insulin insensitivity or reduced sensitivity, combined with comparatively reduced insulin emission which in some cases becomes complete. The imperfect openness of body tissues to insulin almost unquestionably involves the insulin receptors in the cell membranes. Nevertheless, the exact defects are not known yet.

At the start, insulin production is only somewhat impaired in type?2 diabetes, so oral medication, often prescribed in a variety of combinations, can be taken to improve insulin production, to regulate excessive release of glucose by the liver and to soothe insulin resistance to some extent as well. At the same time, to diminish the symptoms of diabetes. But if you do not act fast, the story can be completely different.