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FDA Approves Once-Weekly Dulaglutide for Type 2 Diabetes

 Miriam E. Tucker


The US Food and Drug Administration (FDA) has approved dulaglutide (Trulicity, Eli Lilly & Co), as a once-weekly injection for the treatment of type 2 diabetes.
A member of the glucagon-like peptide-1 receptor agonist class, dulaglutide joins liraglutide (Victoza, Novo Nordisk), exenatide (Byetta, AstraZeneca/Bristol-Myers Squibb), and albiglutide (Tanzeum, GlaxoSmithKline), on the US market.
Once-weekly dulaglutide was approved based on 6 clinical trials involving a total of 3342 patients who received the drug. It was studied as a stand-alone therapy and in combination with metformin, sulfonylurea, thiazolidinedione, and prandial insulin.
In one trial the once-weekly dulaglutide was non-inferior to daily liraglutide and in another it topped the oral dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin (Januvia, Merck).
The most common side effects observed in patients treated with dulaglutide were nausea, diarrhea, vomiting, abdominal pain, and decreased appetite.
Dulaglutide should not be used to treat people with type 1 diabetes, diabetic ketoacidosis, or severe abdominal or intestinal problems, or as first-line therapy for patients who cannot be managed with diet and exercise.
As with others in its class, dulaglutide's label will include a boxed warning that thyroid C-cell tumors have been observed in rodents but the risk in humans is unknown. The drug should not be used in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2.
The FDA is requiring Lilly to conduct the following postmarketing studies for dulaglutide:
•  A clinical trial to evaluate dosing, efficacy, and safety in children
•  A study to assess potential effects on sexual maturation, reproduction, and central nervous system development and function in immature rats
•  An MTC case registry of at least 15 years duration to identify any increase in MTC incidence with the drug
•  A clinical trial comparing dulaglutide with insulin glargine on glycemic control in patients with type 2 diabetes and moderate or severe renal impairment
•  A cardiovascular outcomes trial to evaluate the drug's cardiovascular risk profile in patients with high baseline risk for cardiovascular disease.
The FDA approval also comes with a Risk Evaluation and Mitigation Strategy, including a communication plan to inform healthcare professionals about the serious risks associated with the drug.





Statins And Diabetes: A Clearer Picture Emerges


Larry Husten 

In recent years, the medical community has become increasingly aware that taking statins can result in slightly higher glucose levels, and this can lead to a diagnosis of diabetes in a small but statistically significant number of people. But it has been unclear whether the diagnosis of diabetes in people taking statins also places them at increased risk for the microvascular complications linked to diabetes. Now, an observational study published in the Lancet Diabetes & Endocrinology finds that among people newly diagnosed with diabetes, statin users are less likely than nonusers to develop most of these complications. (The beneficial effects of statins in reducing macrovascular complications — cardiovascular disease — in diabetics and others is well established in people at high risk for these events.)
Danish researchers examined the rate of microvascular outcomes in more than 15,000 statin users who developed diabetes and 47,000 nonusers of statins who developed diabetes. Over a median follow-up of 2.7 years, statin users had a 40% reduction in the risk for developing retinopathy (hazard ratio 0.60, CI 0.54–0.66, p<0.0001), a 34% reduction in the risk for diabetic neuropathy (HR 0.66, 0.57–0.75, p<0.0001), and a 12% reduction in gangrene of the foot (HR 0.88, 0.80–0.97, p=0.010). There was no significant difference in the rate of diabetic nephropathy (HR 0.97, 0.85–1.10, p=0•62). The overall results were similar after adjusting for differences between the groups. In rough accord with previous research, the Danish researchers observed that statin users had a 17% increase in the risk for developing diabetes.
The authors conclude: “Whether or not statins are protective against some forms of microvascular disease, a possibility raised by these data, and by which mechanism, will need to be addressed in studies similar to ours, or in mendelian randomization studies…. Ideally, however, this question should be addressed in the setting of a randomized controlled trial.”
Commenting on the study, Darrel Francis offered an overview of the risks and benefits of statins: “For every 1000 primary prevention patients randomized to statin, 5 patients gain a diagnosis of diabetes, while 5 patients are saved from death, 10 from nonfatal myocardial infarction, and 6 from stroke. Some people find this a good deal, but others a are cautious because of the justified fear of diabetes.”


Global Diabetes Epidemic Hampers Tuberculosis Control



Jessica Berman

The growing number of Type 2 diabetes cases worldwide will make it difficult to control and eliminate tuberculosis. Experts have found a connection between the two diseases, reminiscent of HIV and TB.
For reasons that are still unclear, Type 2 diabetes increases the risk of developing tuberculosis. In a series of articles in the journal The Lancet Diabetes and Endocrinology, researchers report that 15 percent of adult TB cases worldwide are due to diabetes, translating to more than 1 million infections. 
More than 40 percent of diabetes-associated TB cases are in India.
Renout van Crevel, a researchers and professor of international health at Nijmegen Medical Center in the Netherlands, said diabetes triples the chances of developing tuberculosis. With diabetes reaching epidemic proportions, van Crevel said that will make TB control efforts increasingly difficult.
“There are now 380 million diabetes patients worldwide. Twenty years from now it will be 580 million. And this increase is especially taking place in Africa, where the incidence of TB is the highest,” said van Crevel.
Van Crevel likens the relationship between diabetes and TB to that of HIV and tuberculosis. Having one disease increases the risk of acquiring the second.
With HIV, a severely compromised immune system sets the stage for an active TB infection.
With diabetes, the cause of the increased risk is less clear. Van Crevel suggested something is happening metabolically in those with Type 2 diabetes that makes them vulnerable to tuberculosis.
Once infected with TB, diabetics also are much harder to treat, according to Van Crevel.
“TB treatment -- there is more failure, there is more relapse, there is more toxicity when the patient is also suffering from diabetes. So for the individual patient, there is more issues when these two diseases come together, just like HIV and TB let us say.”
But the news is not all bad. Experts report public health efforts to help patients prevent and control diabetes with good diet and exercise could potentially reduce the number of TB cases by 15 percent or more by 2035 over current expected reductions in the tuberculosis rate.