The Role of DPP-4 Inhibitors in Type 2 Diabetes Mellitus

This article discusses the use of dulaglutide and sitagliptin in the management of type 2 diabetes. Dulaglutide is a recombinant GLP-1 Fc fusion protein, which acts by linking GLP-1 analog peptide and a variant of lgG4 Fc fragments in humans. As such, the analog of GLP-1 has posed effects and has shown elevated efficacies in the management of type 2 diabetes. The primary efficacy in the baseline of HbA was altered during the end of 52nd week. The objective of secondary efficacy included a change in HbA during the end of the 26th and 104th week. The percentage of patients achieved HbA targets ranged between 7.5% to 6.5% in a central laboratory and the body changed significantly. However, current treatment majorly focuses on increasing

The mainstay of type 2 diabetes medication is Metformin due to the cost, safety of the medication and limitied side effects. Metformin reduces glucose levels through two pathways; it reduces hepatic glucose production and increases the insulin tissue sensitivity. Monotherapy is normal for this medication; however, it can be utilized in combination with other medications. Metformin used in conjunction with Sodium glucose cotransporter provides a greater control over the level of glucose in the body due to the reduction of glucose production, increase in sensitivity, reduction of reabsorption of glucose and the excretion of glucose through the kidneys, basically the glucose control is through 4 different pathways making it a synergetic effect on diabetes type 2. According to Inzucchi et al.(2016), the combination of these medications helped patients reduce their overall A1c (0.5-1.0), lose weight (2kg) and a reduction in their blood

DPP-4 inhibitors medications work by helping to reduce glucose levels, but generally not a lot. A positive however is they don't cause weight gain. These medications include Sitagliptin, Saxagliptin and Linagliptin.

Coadministration of glimepiride and metformin has been used to achieve glucose control. This combination might be a suitable alternative for patients with whom compliance with a multiple medication regimen is difficult. An earlier study found that fixed dose combination of glimepiride & metformin is effective and safe in patients with type 2 DM. Recently one more strength of combination tablet, glimepiride 2 mg + metformin 500 mg was developed.

In non-diabetic people around 180 g per day of glucose is freely filtered by the kidneys but nearly all is reabsorbed by SGLT2, with loss in urine occurring only when plasma glucose exceeds a threshold for reabsorption (Gerich, 2010). In type 2 diabetes, even when hyperglycemia occurs, filtered glucose continues to be reabsorbed, leading to persistently elevated blood glucose concentrations (Janssen-Cilag,2012 and Bristol-Myer Squibb,2012). By selectively and reversibly inhibiting SGLT2, dapagliflozin and canagliflozin lower plasma glucose levels through decreased reabsorption of glucose and increased urinary glucose excretion, creating a diuretic effect. The current global markets of all SGLT2 are depicted in (Figure 1).

Diabetes mellitus is due to a lack of insulin production from beta cells in the pancreas resulting in an insufficient amount of insulin to be able to regulate the bodies blood sugar levels. This causes insulin resistance which is the inability of cells to respond properly to insulin in the fat tissues, muscles and liver. What normally happens in the liver is insulin suppresses glucose synthesis if the levels in the blood are to high and causes the cells especially in the liver to take in glucose and store it as glycogen. However during insulin resistance the liver continuously breaks down glycogen in glycogenolysis to release glucose into the blood. Once liver is saturated with

Patients diagnosed with diabetes have elevated HbA1C levels of 6.5% or higher. The American Diabetes Association recommends a target of < 7% for most patients3 with diabetes to be considered controlled. Type 2 Diabetes patients usually begin with monotherapy oral medication, such as Metformin along with diet and exercise to decrease blood glucose levels and HbA1C levels. Unfortunately, monotherapy is not effective in many patients and they soon add a second therapy. A sulfonylurea, such as Glyburide, is a second-line drug in the treatment of diabetes because it “enhances insulin secretion”3 unlike metformin which “increases insulin sensitivity.”3

The newest class of antidiabeteic medications to be approved for use in the United States is the glucagon-like- peptide-1 agonists (GLP-1). There are two drugs in this class that are currently available, exenatide (Byetta, Bydurian) and liraglutide (Victoza) (LexiComp, 2014). These medications mimic the actions of endogenous GLP-1. Endogenous GLP-1 is secreted from the L-cells in the colon and ileum in response to the ingestion of nutrients (Ryan, Foster, & Jobe, 2011, p. 794). GLP-1 has a half-life of 2 minutes due to the action of the DPP-4 enzymes. GLP-1 agonists overcome this issue by having an altered structure that renders them less susceptible to DPP-4 enzymatic degradation thus

Sodium linked Glucose Co- Transporter-2 (SGLT-2) inhibitors form a new class of agents that act on the kidney by competitively blocking the SGLT-2 channels. These agents are approved by FDA to be used as monotherapy or in combination with Metformin, Sulphonylurea (SU), Pioglitazone, or insulin. The ADA practice guidelines have added SGLT-2 inhibitors as the first add on to Metformin along with other drugs like SU, Dipeptyl Peptidase 4 (DPP4) inhibitors, thiazolidinedione and basal insulin. SGLT-2 inhibitors also finds a place as a second add on drug after 2 of the other drugs are

Overall it was collected that a number of type 2 diabetes drugs lowered A1C and CV risk at roughly the same degree, with the major differences noted in route of administration, side effects, and price, rather than efficacy. Most of the oral antidiabetics in question showed no difference on a 95% confidence interval in regard to reduction of all cause mortality, and cardiovascular mortality. Based on meta-analysis of these studies, it can be suggested that monotherapy with metformin is a good first line option, however other agents may prove to be similarly efficacious and appropriate for use in select patient populations as there was no notable difference suggested in reducing cardiovascular outcomes between the drug classes.

Do’s and don’t related to drug therapy/ administration: Before taking this medication check for your radial pulse for a full minute. If your heartbeat is less than 60 beats per minute do not take the dosage and contact your provider. This drug should be taken once a day at the same time. This drug can be taken with or without food. If taken with food avoid taking it with foods that are rich in fiber (oats, raspberries, artichokes, lentils and

Instruct the patient to take the medication as prescriber directed. If missed a dose take the missed dose as soon as remembered and following doses should be evenly spaced. Also advice the patient that the dose takes weeks till therapeutic effects are achieved. Do not discontinue or reduce dose during this time since there are side effects. Some of the withdrawal effects include; dizziness; nausea; vomiting; GI upset; trembling; or uncontrolled movements of mouth, tongue, or jaw.

It is clear from Figure 9 that the conventional release system has some limitations. Frequent administration is required because of the short half-life[38,39]. However, the release rate of the controlled release system, can be kept at a expected level for a relatively long period of time. It can avoid drug plasma level fluctuations and stabilize plasma level[38]. In addition,

Nitroglycerin is well absorbed through the oral, buccal and sublingual mucosa. Nitroglycerin administered orally is rapidly metabolized leading to decrease bioavailability. Nitroglycerin is metabolized rapidly through the liver as well as enzymes in the bloodstream, and has a half-life of 1-4 minutes. For acute angina, 0.4 mg is administered sublingual. In the event the initial dose does not decrease the pain, a second dose can be administered sublingually after 5 minutes up to a third dose. If the pain persists after administering the third dose, the patient is instructed to call 911. Topical doses can be administered 0.5-2 inches from the site of administration

It becomes really challenging to achieve normal glucose level in patients with diabetic & CKD. The development & progression of CKD result in