The incretin-diabetes link is crucial in the regulation of blood sugar in the body. Incretins are gastrointestinal hormones that, upon eating, are released to help insulin production, and slow digestion and the absorption of nutrients into the blood. This limits the chance of blood sugar spikes, by decreasing the amount of glucagon excreted by the pancreas. GLP-1 (glucagon-like peptite-1) and GIP (gastric inhibitory peptide) are two such incretins. GIP is then kept in balance by the release by DPP-4 (dipeptidyl peptide-4 enzyme). The incretin and diabetes problem is that diabetics are often deficient in these hormones. In this case, DPP-4 levels go up, putting the system out of balance and leading to high blood glucose levels.
Diabetes, Incretin, and The Related Drugs
In recent years, two types of treatment were developed to rebalance this delicate system. One method synthesized GLP-1, which must be injected. The two long-lasting medications approved for use in the U.S. by the Food and Drug Administration (FDA) are Byetta (exanatide) and Victoza (liraglutide). The other method is to inhibit the production of the DPP-4 enzyme that stops the production of the incretins. These DPP-4 inhibitors are available as tablets, taken orally. The FDA-approved DPP-4 inhibitors include Januvia (sitagliptin), Onglyza (saxagliptin) and Trajenta (linagliptin). Januvia was the first to be approved, and is the best known. A “mimetic” is another term for synthesized incretin. Diabetes patients who inject the incretin mimetic Byetta can expect lower blood sugar along with some weight loss, but may experience side effects such as hypoglycemia (due perhaps to an incorrect dosage), nausea, and more rarely, inflammation of the pancreas. Victoza is a longer-acting synthesized incretin; diabetes patients may be able to keep blood sugar more balanced through the day with less risk of hypoglycemia and other side effects. Exenatide-LAR, approved in January 2012, is a once-weekly injection, but is otherwise similar to Victoza. Januvia, the DPP-4 inhibitor, lowers blood sugar and A1c levels, but can cause cold-like symptoms, headaches, nausea, diarrhea and abdominal pain. Certain people may also experience allergic reactions, or swelling of the hands, feet or legs. Onglyza and Trajenta have similar benefits and side effects, though unlike Januvia and Onglyza, Trajenta may be safer for those with renal problems, as it is not excreted through the kidneys. However, patients with diabetic acidosis are advised not to take Trajenta.
Incretin Therapy: What are the Alternatives?
Though research continues to develop safer and more efficient diabetes medications, there are still serious side effects which must be considered when deciding on diabetes treatment. This is also true in the case of DPP-4 inhibitors and synthesized incretin. Diabetes patients should only consider these drugs if they cannot control their blood sugar with diet and exercise. There are also herbal supplements that lower blood glucose and increase insulin sensitivity, such as bitter melon, gymnema sylvestre and mulberry leaves.
