Endocrinologist Robert Cuddihy, MD, joined Sanofi US over a year ago to be the company’s Vice President and Medical Diabetes Head in the United States. He is responsible for developing and executing the US strategy for Sanofi’s Diabetes Division, including pharmaceuticals, devices, and other technologies. He previously served as the medical director for several organizations, including the International Diabetes Center-Park Nicollet in Minnesota.
Diabetes Health recently spoke with Dr. Cuddihy about Lantus. We began by discussing the sanofi ORIGIN trial, a six-year study that examined the use of Lantus (insulin glargine) in people with diabetes who are at risk for cardiovascular problems.
DH: Can you elaborate on the ORIGIN study and its significance for prediabetes and type 2 diabetes?
Dr. Cuddihy: ORIGIN was a six-year randomized clinical trial designed to assess the effects of treatment with Lantus versus standard care on cardiovascular (CV) outcomes. The study involved over 12,500 participants worldwide with prediabetes or early type 2 diabetes and high CV risk, with 6,264 participants randomized to receive Lantus titrated to achieve fasting normoglycemia. There were two coprimary composite cardiovascular outcomes. The first was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second was a composite of any of these events, a revascularization procedure (cardiac, carotid, or peripheral), or hospitalization for heart failure. Additionally, there were adjudicated outcomes, including a composite microvascular outcome, incident cases of diabetes in participants without baseline diabetes, all-cause mortality, and new or recurrent cancers.
The significance of this study is that ORIGIN investigated the use of Lantus in a population in which insulins are not typically used, providing new data on the potential benefits and risks of initiating Lantus therapy earlier in the course of diabetes. Of the patients on Lantus, 58 percent were free of symptomatic hypoglycemic episodes for the entire duration of the study. Results also showed that Lantus delayed progression from prediabetes to type 2 diabetes by 28 percent.
DH: Is Lantus now being considered for prediabetes as an initial therapy?
Dr. Cuddihy: Lantus is the only 24-hour insulin approved exclusively for use once a day and remains the number one prescribed insulin. We cannot comment on future indications for Lantus.
DH: Are some healthcare professionals using Lantus off label for prediabetes?
Dr. Cuddihy: We cannot comment on the off-label use of Lantus.
DH: How many type 1 and type 2 patients are estimated to be on glargine insulin?
Dr. Cuddihy: Lantus remains the number one prescribed insulin. To date, there have been 47 million patient years of treatment exposure to Lantus. The majority of patients are living with type 2 diabetes.
DH: Sanofi has released new data about combining metformin with Lantus. What are the benefits associated with combining metformin and Lantus, and how is this different from other combination therapies?
Dr. Cuddihy: The EASIE trial was a multicenter, international, randomized, open-label, six-month study that compared once-daily Lantus with sitagliptin once daily, as add-on therapy to metformin, in insulin-naive people with early type 2 diabetes. The study successfully demonstrated that people with early type 2 diabetes uncontrolled on metformin demonstrated superior A1C reduction with Lantus versus sitagliptin. We cannot comment on how this combination is different from others; however, the EASIE study adds valuable data to further strengthen the efficacy profile of Lantus when initiated early in the treatment pathway after metformin.
DH: Lyxumia in combination with basal insulin has also helped patients with type 2 diabetes lower their blood sugar. What is Lyxumia and how does it work with basal insulin to lower blood sugar?
Dr. Cuddihy: Lixisenatide is a once-daily injectable GLP-1 receptor agonist that is currently in late stage clinical trials, to be used alone, in combination with basal insulins, and/or in combination with oral antidiabetic agents. The Get Goal Duo1 trial is a randomized, double-blind, placebo-controlled study assessing the efficacy and safety of once-daily lixisenatide versus placebo, in combination with glargine and OADs (mostly metformin). The study demonstrated that lixisenatide significantly reduced A1C in combination with optimally titrated Lantus, with a significant improvement in post-prandial glucose and beneficial effect on body weight.
As an agent within the GLP-1 receptor agonist class, lixisenatide stimulates glucose-dependent rise in insulin secretion and suppresses glucagon, can have an effect on slowing of gastric emptying (helping to lower post-prandial glucose excursions), and can result in early satiety from both direct CNS effects and delayed gastric emptying.
DH: There have been some concerns about Lantus and cancer risk. However, a new independent study just stated that “no increased risk of cancer was found with Lantus in new European and US observational studies.” How did the independent researchers conclude this?
Dr. Cuddihy: A large-scale epidemiological program conducted by independent researchers in the northern European countries, at Kaiser Permanente in Northern and Southern California, and at the University of North Carolina, provided further evidence that there was no increased risk of cancer in people with diabetes treated with Lantus. These new results reinforce the established safety profile of Lantus, complementing the existing wealth of data already available resulting from more than 80,000 patients enrolled in clinical trials and over 47 million patient-years of treatment exposure to Lantus.
The Northern European Database Study is the largest of its kind, with 447,821 patients using insulin and over 1.5 million person-years of observation. This observational study found no evidence of an increased risk of breast cancer in women, prostate cancer in men, and colorectal cancer in men and women in users of Lantus versus other insulins.
The main analyses of this US database study (using the Northern and Southern California Kaiser Permanente diabetes registries, which included 115,000 patients with median duration of 1.2 years for Lantus use and 1.4 years for neutral protamine Hagedorn among all insulin users) showed no association between use of Lantus and increased risk of breast cancer, prostate cancer, or colorectal cancer. Furthermore, there was no association between Lantus use and increased risk of all cancers combined.
In addition to the Northern European and US epidemiology studies, the ORIGIN study demonstrated that there was no association between Lantus and increased risk of any cancer. Neither analysis of all cancers combined nor analysis of any organ-specific type of cancer suggested an increased risk for the users of Lantus.
Additional results are expected from a third observational study, the International Study of Insulin and Cancer (ISICA), which will be completed in 2012.
DH: Thank you for your time, Dr. Cuddihy.