Drugmakers angle for advantage in treating diabetes
Obesity and longevity have helped make diabetes an epidemic in much of the world, and drugmakers are jockeying to make sure their medicines are used early and often.
Companies including Sanofi and Eli Lilly aim to introduce new classes of drugs that could further extend treatment options, and potentially their market share.
Once diagnosed, people with type 2 diabetes are commonly treated with generic drugs, followed by several different classes of branded pills, injected medicines and eventually insulin.
Some major pharmaceutical players are trying to gain an earlier foothold in that succession of treatment as the market for such drugs has grown dramatically, with global incidence of diabetes reaching nearly 350 million cases over the last 30 years.
At the American Diabetes Association meeting in San Diego this week, Boehringer Ingelheim Pharmaceuticals and Lilly promoted their new oral drug, Tradjenta, as a better option for a patient’s next line of defense after generics. Tradjenta, also known as linagliptin, is a member of a class of oral drugs known as DPP-4 inhibitors.
“Our focus is to be the first product to be added to metformin,” said John Smith, head of clinical development and medical affairs at Boehringer. Metformin is the generic pill initially prescribed for many diabetes patients.
That goal may be helped by the fact that another class of branded diabetes drugs may be falling out of favor. Since patients now live for decades with diabetes, the safety profile of treatments has become even more important. Drugmakers face increased scrutiny of cardiovascular and cancer risks.
“Patients with type 2 diabetes are living longer, so there is a higher incidence of other problems,” said Dr. Joel Zonszein, director of the clinical diabetes center at Montefiore Medical Center in New York.
CONCERNS
Top-selling diabetes drug Actos, marketed by Takeda Pharmaceutical Co , is a high-profile example of the safety concerns. Recent data on the drug, with nearly $5 billion in annual sales, linked it to increased risk of bladder cancer if used for more than a year.
U.S. health officials added that information to the drug’s label, while France and Germany suspended Actos sales.
Actos is a thiazolidinedione — shortened to TZD or glitazone — designed to lower the body’s insulin resistance, the underlying problem for people with type 2 diabetes.
Earlier versions of glitazones caused serious liver damage for some people and were withdrawn from the market. Avandia, a member of the same class sold by GlaxoSmithKline , has been linked to heart risks.
For Actos, “it is too early to say” whether the preliminary findings have had an impact on sales, said Dr. Robert Spanheimer, Takeda’s vice president, medical and scientific affairs. He said full results from the Actos safety trial will be available in 2013.
ORAL DRUGS SEEN AS MOST CONVENIENT
Global sales of diabetes medicines totaled $35 billion last year and could rise to as much as $48 billion by 2015, according to research firm IMS Health, driven by increased prevalence and treatment, especially in countries such as China, India, Mexico and Brazil.
“There is a large amount of people who don’t know they have diabetes,” said Dr. Stuart Weinerman, chief of endocrinology at North Shore-Long Island Jewish Health System in New Hyde Park, New York. “There is an even larger group of people that have diabetes and don’t control it adequately.”
IMS also forecast growing use of oral diabetes medicines due to their convenience and efficacy.
“The aim is to preserve the option of oral therapy for as long as possible,” said Boehringer’s Smith.
Boehringer is also developing a member of a new class of drugs known as SGLT2 inhibitors, which are designed to block glucose from being absorbed into the bloodstream through the kidneys, allowing more sugar to be excreted with urine.
New data on another experimental SGLT2 inhibitor, dapafliglozin from Bristol-Myers Squibb and AstraZeneca , showed that it was effective in a two-year study. But more bladder and breast cancers were found in patients treated with the drug.
“The probability of these drugs causing cancer is very, very low … the duration of the trials was too short,” said Zonszein.
Lilly also featured information on Byetta, an injectable GLP-1 drug co-marketed with Amylin Pharmaceuticals , which is suing Lilly over its deal with Boehringer.
Amylin presented data at the conference showing no significant link between use of Byetta and heart rhythms, which is important since U.S. regulators have asked for a heart risk trial of the company’s once-weekly GLP-1 drug, Bydureon.
That data is expected soon and Amylin said it plans to refile for U.S. regulatory approval of Bydureon in the second half of this year.
Drugmakers are also working on improved versions of insulin, the blood-sugar controlling hormone that is missing in people with type 1 diabetes and can be needed by patients with the more common type 2 diabetes.
Novo Nordisk , the world’s biggest insulin producer, showed that its experimental long-acting insulin, degludec, lowered blood sugar levels with less risk of hypoglycemia, compared with Sanofi’s Lantus.
Degludec is formulated with spacer molecules to provide a more steady rate of absorption than current insulins, said Alan Moses, Novo Nordisk’s chief medical officer.
“It lines up like pearls on a string … the insulin just basically drops off one molecule at a time from the ends,” he explained.
Sanofi’s diabetes division head, Dennis Urbaniak, said the French drugmaker aims to hold its market share with Lantus.
“Lots of other folks are trying to change that position,” he said.
ADA: Intensive Tx No Better than Good Routine Diabetes Care
SAN DIEGO — Screening and early intensive management of type 2 diabetes may hold little benefit beyond usual care, perhaps because of more aggressive routine practice, researchers suggested.
Intense managment of glucose, lipids, and blood pressure for screen-detected cases in the randomized ADDITION trial modestly reduced cardiovascular events by 12% and raised overall survival by 9% over roughly five years, Simon J. Griffin, MD, of Addenbrooke’s Hospital at the University of Cambridge, England, and colleagues found.
But neither advantage reached statistical significance compared with the outcomes of routine primary care by Dutch, Danish, and British clinicians, the group reported here at the American Diabetes Association meeting and simultaneously online in The Lancet.
The first cardiovascular event incidence rate was 7.2% with intensive treatment versus 8.5% with usual care (HR 0.83, 95% confidence interval 0.65 to 1.05); all-cause mortality occurred in 6.2% and 6.7%, respectively (HR 0.91, 95% CI 0.69 to 1.21).
These results, reiterating those presented at the European Association for the Study of Diabetes meeting last fall, were again seen as an overall positive for early diabetes treatment regardless of intensity.
“Any form of early therapy seems to pay dividends when compared with either later detection or delayed diagnosis and intervention,” David Kendall, MD, the ADA’s chief scientific and medical officer, told MedPage Today.
The trial couldn’t be definitive about the clinical benefit of screen detection of diabetes in the context of current clinical practice, David Preiss, MRCP, and Naveed Sattar, PhD, both of the University of Glasgow, Scotland, cautioned in a commentary accompanying the Lancet paper.
“However, the substantial improvements in blood pressure and cholesterol observed in the routine care group suggest that early diagnosis and treatment of diabetes according to current guidelines is likely to be beneficial,” they wrote in the commentary.
The usual care group achieved an 11.7 mm Hg reduction in systolic blood pressure and 1.2 mmol/L lower LDL with treatment by standard European guidelines, reductions that were nearly as good as the 13.7 mm Hg and 1.3 mmol/L reductions with intensive management although reaching statistical significance for a difference.
European guidelines don’t recommend routine screening for diabetes, unlike ADA guidelines, which recommend screening every three years for all adults over age 45 or regardless of age for those overweight, obese, or with at least one risk factor.
But national guidelines in the three northern European countries involved got more aggressive on treatment for diabetes patients during the trial.
Thresholds for antihypertensive treatment dropped from a systolic blood pressure of 140 to 155 mm Hg in 2001 at baseline to 130 to 140 mm Hg at follow-up; cholesterol treatment thresholds fell from 5.0 to 6.0 mmol/L to 4.5 mmol/L.
Diabetes treatment goals changed to include 6.5% in the A1c target range in some countries, although remaining largely stable overall.
Those unexpected changes may have undermined the trial’s ability to detect significant benefits from intensive managment, Preiss and Sattar suggested.
By the end of the trial, “the treatment groups were similar in terms of allocated treatments (such as statins) and had similar prevalence of glycemia and cardiovascular risk factors, with the result that achieving the target of a 30% reduction in cardiovascular events with intensive therapy became unlikely,” they wrote in the Lancet.
ADDITION — the Anglo-Danish-Dutch study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care — included 3,057 patients (age 40 to 69) who screened positive for diabetes at primary care practices in Britain, the Netherlands, and Denmark.
Patients randomized to intensive treatment received:
Antihypertensive treatment starting with an ACE inhibitor at a blood pressure of 120/80 mm Hg or higher, with directions to intensify treatment for blood pressures of 135/85 mm Hg or greater
Lipid-lowering medication at an LDL of 3.5 mmol/L (135 mg/dL) or higher with intensification for those at or above 4.5 mmol/L (174 mg/dL)
Diabetes medications targeting a hemoglobin A1c of 6.5% or less
At the mean 5.3 years of follow-up, all the individual components of the primary cardiovascular event outcome (cardiovascular death, MI, stroke, and revascularization) tended to favor intensive therapy numerically, although without statistical significance.
The researchers pointed to the apparent divergence of cardiovascular event rates beyond four years, suggesting that five years of follow-up may be insufficient if the benefits of more intensive therapy accrue over the long term as in the UKPDS study.
But Griffin’s group cautioned that they could not rule out chance findings.
The low event rates in both groups — half what had been expected — left the trial underpowered, potentially obscuring benefit from intensive therapy, the commentary noted.
Also, participating primary care practices may have been those more motivated to improve their quality of diabetes care, “such that the routine care delivered in the trial might not be representative of routine care elsewhere,” it added.
The quality of care in the routine primary practice group may just have been too good, the researchers agreed.
Diet, Metformin Cut Medical Cost for Prediabetes Patients
People with prediabetes can save thousands of dollars in medical costs by taking the diabetes drug metformin or making lifestyle changes, a new study shows.
Treatment with the inexpensive drug metformin, which lowers blood sugar levels, reduced costs by $1,700 over a decade, the researchers say. Intensive lifestyle changes, such as participating in tailored weight loss and exercise programs, saved $2,600 per person.
The study also showed that people who ate right and exercised had the highest scores on quality-of-life questionnaires that measure physical and mental functioning.
The cost savings are in line with other standard prevention strategies such as childhood immunizations and beta-blocker treatment in people who have had a heart attack, says William Herman, MD, professor of internal medicine at the University of Michigan, Ann Arbor.
The interventions should be offered to all people at high risk of developing diabetes, he tells WebMD. About 79 million Americans have prediabetes and are at high risk, according to the CDC.
Herman presented the study here at the annual meeting of the American Diabetes Association.
The cost-savings analysis comes from seven years of follow-up to the three-year study called he Diabetes Prevention Program (DPP). The study was halted early when both metformin and lifestyle changes far outperformed placebo.
The DPP showed that 10 years of treatment with metformin lowered the risk of developing diabetes by 18%, while lifestyle changes reduced the chance by 34%.
The economic analysis showed that lifestyle strategies were more expensive to implement, costing about $4,500 per person over 10 years. Metformin cost about $2,000 over a decade.
The increased cost of lifestyle programs was offset by the $2,600 savings in medical care, which included money spent on doctor and hospital visits as well as on drugs, Herman says.
When dollars spent were weighed against money saved, metformin saved $30 per person over 10 years and the lifestyle intervention cost $1,500.
While no price tag can be placed on improved physical and mental well-being, the researchers also weighed in the finding that lifestyle changes were associated with better quality-of-life scores than metformin, Herman says.
“Compared to doing nothing, the metformin intervention is cost-saving for diabetes prevention, and the intensive lifestyleintervention, though not saving dollars over 10 years, is extremely cost-effective,” he says.
New Approach for Diabetes Prevention
The new analysis “is important because as soon as DPP was published, people said, ‘This is great but we don’t have the resources,’” Herman says.
Only one in 10 common prevention strategies — prenatal care and flu shots, for example — actually saves money, he says.
The cost savings in the new study included lower costs for doctor and hospital visits as well as for drugs.
“I’m really stunned by these findings,” says James Meigs, MD, of Massachusetts General Hospital in Boston. “They could revolutionize the way we approach diabetes prevention.”
Most people prefer making exercise and dietary changes to taking a drug, says Meigs, who was not involved with the research.
In the study, the focus of the lifestyle intervention program was on losing and maintaining a 7% loss in body weight and 30 minutes a day of brisk walking, five times a week, or its equivalent, according to Herman.
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