Diabetes Type 2 Case Scenario

Diabetes Type 2 Case Scenario

Treatment Options, Guidelines and Recommendations

Type 2 diabetes mellitus is a chronic condition of considerable economic and clinical burden globally. The disease is also typified by an intensifying deterioration in β‐cell function. As a result, the patient progressively loses their glycemic control. Control of a patient’s blood glucose levels therefore constitutes a fundamental objective of therapy in type 2 diabetes mellitus, given the causal link between reduced glycemic control and the development of various mascrovascular as well as microvascular complications. From the scenario given, Patient A, A 70-year old Caucasian male, in currently on metformin 850mg, Gliclazide 40mg and Linagliptin 5mg for blood-glucose control. How, his current medication does not give him adequate glycemic control, based on his recent blood results.  The NICE guidelines for the management of type 2 diabetes in adults recommend the use of a monotherapy as an initial drug treatment.

Metformin is a recognized first-line medication for lowering glucose levels in type 2 diabetes patients. Patient P has been prescribed Metformin 850mg as his first-line of treatment for blood-glucose control. In the event that the use of metformin monotherapy cannot control glycated hemoglobin, the NICE guidelines recommend the use of a second agent such as sulfonylureas. However, despite the drug being recommended in first line therapy, it is known to cause lactic acidosis a rare but serious complication caused by overdose of metformin. This condition presents with decreased blood pH, electrolyte disturbances, and elevated blood lactate levels. This condition further complicates to cause significant renal damage, renal hypo-perfusion and renal damage. However, metformin is recommended for its ability to offer renal nephrotoxicity protection, if the patient is on therapeutic dosage. It reduces albuminuria in patients with diabetes (Rafieian-K & Nasri, 2012).

Already, Patient A is on Gliclazide 40mg which is a sulfonylureas agent.  However, monotherapy and dual therapy fail to control blood glucose levels in a patient with type 2 diabetes a triple therapy may be used. Alternatively, it may be necessary to include a treatment combination that also constitutes insulin (NICE, 2015). Some of the adverse effects related to gliclazide include changes in vision, sweating, bradycardia, confusion due to electrolyte imbalance and elevated liver enzymes, as it is an inducer. The drug also interacts with alcohol to cause intolerance. Other medications known to interact with gliclazide include antidepressants, aspirin, propranolol, oral contraceptives and rifampin.

Already, patient A is on Linagliptin 5mg. it is a recommended drug for diabetic old patients. However, this three drug therapy is not effective as the patient’s glycated haemoglobin is not under control.  Linagliptin is however not effective in reducing the fasting blood sugars since the glucagon-like proteins increased by this drug is secreted in the small intestine, stimulated by food. Linagliptin is known to cause breakdown of the low density lipoproteins, with minimal or no effect on the high density lipoproteins. It therefore causes hyperlipidaemia in diabetic patients. A triple therapy has proven to be ineffective in the management of Type 2 diabetes in adults and for this reason, NICE recommends a combination therapy that consists of metformin in combination with a sulfonylurea. Some of the adverse effects related to

Additionally, a GLP-1 (glucagon-like peptide-1) nimetic may also be used. This recommendation is for patients whose BMI is at or above 35 kg/m² or higher. Patient A has a BMI of 24.33 kg/m^2. For use of GLP-1 mimetic therapy, it must be demonstrated that the patient seen his HbA1c levels reduce by 11mmol/mol, along with a minimum weight loss of 3% within the duration of 6 months (NICE, 2015). In the event that the patient cannot tolerate metformin, and in case a dual therapy of 2 oral drugs fails to control a type 2 diabetes patient’s HbA1c levels, it may be necessary to switch to an insulin-based therapy (NICE, 2015). Additionally, the NICE guidelines provides that in offering a GLP-1 mimetic alongside an insulin therapy, there is need to seek ongoing support and specialised advice and care form a multi-disciplinary team. Exenatide, a recommended second generation drug of this class is known to cause acute kidney injury to diabetic patients, due to its effects on reduced fluid intake, excessive fluid loss via diarrhoea and vomiting. Overdose complications of this disease include loss of liver function, hypoglycaemia and gut symptoms.

Evidence behind Recommendations

Glucagon-Like Peptide-1 Receptor Agonists including dulaglutide, liraglutide, albiglutide, and exenatide are recommended for inclusion in dual therapy of patient A. According to Bunck et al., (2009), the use of this class of drugs in combination with insulin has similar effects on lowering A1C, and even higher beneficial effects in beta cell functioning. This class of agents is also known to have low risk for hypoglycaemia. Glimepiride in a sulfonylurea similar to glipizide, but has beneficial effects in contrast to glipizide. Glimepiride is known to be weight neutral, while glipizide is associated with weight gain of approximately 2Kgs. Weight gain is a risk factor for diabetic patients, especially because it is associated with increased insulin resistance, thereby exacerbating the complications.

Basal Insulin is an injectable diabetic agent. It is considered the most efficient in regulating levels of blood sugar, for patients who have failed to benefit from the oral combination therapy. Basal insulin is known to cause weight gain, but when used as a combined therapy with exenatide, a glucagon-like peptide receptor agonist, it improves glycaemic control as well as eliminating the risk for hypoglycaemia and weight gain (Buse et al., 2011). It has also been recommended that the patient continues on metformin. The drug is known to have cardiovascular protective effects such as weight loss, reduce LDL cholesterols and increase rate of lipometabolism (Xu et al., 2015), reduce insulin resistance and plasma insulin, and also reduce systolic blood pressure in diabetic patients by deactivating the adrenergic receptors, reducing the intracytoplasmic calcium levels and also via inhibition of the sympathetic drive which is likely when salt is high (Zhou et el., 2017). Moreover, metformin reduces weight gain by reducing hunger perception, and hence less food intake. However, the dosage should not be increased, since he is already getting the maximum dosage recommended of 2500mg/day (Scarpello & Howlett, 2008).

Therefore, in order to increase the effectiveness on reducing the A1C, it is necessary to incorporate basal insulin, a long acting injection and also change gliclazide to glimepiride. Glipizide is an old diabetic agent known to increase weight gain, which is a risk factor for increased resistance to insulin, thereby predisposing Patient A to a higher risk of developing diabetes-related complications.

Formulation(s) recommended

Metformin, which is recommended as the first line drug in management of diabetes, is an oral tablet 500mg. It is absorbed in the in the upper small intestines specifically the duodenum and the jejunum (Graham et al., 2011) into the hepatic blood circulation. Oral drugs have a low rate of absorption, and hence the drug takes longer to be effective. In the absorption and transport of the drug, 50% of it is lost unused, and hence only half of it is used. For this reason, the drug is less likely to cause hypoglycaemia, unless in overdose cases. In addition, it’s oral administration as an oral tablet has potential benefits to the gut system; it helps in bile acid metabolism, delays intestinal absorption of the glucose, stimulates production of enterocytes and also helpful to the microbiota.

Gliclazide 40mg, similarly to metformin, is an oral tablet taken around thirty minutes before the meal. This is done to give time for the slow bioavailability. However, unlike metformin, glimepiride has a 99% binding capacity, and hence very less is lost in the first pass effect. For this reason, gliclazide is likely to cause hypoglycaemia in diabetic patents, especially if the patient skips a meal or involves in a physical exercise that he/she is not used to. As an oral drug, it is known to maintain the weight of the patient, and hence advocated for, in the triple and double therapy management for obese patients. This drug is recommended in double therapy to manage diabetes in the outpatient, since it acts slowly and hence need to take it before eating. Gliclazide is less costly, and hence highly affordable by the patients.

Basal insulin is used as a subcutaneous injection, either on the lower arm, or the stomach. As an injection, it has a higher bioavailability than oral drugs. It is used mainly in the emergency situations, but also in patients with high A1C despite use of duo therapy. The high bioavailability increases the chances to cause hypoglycaemia very fast. Since it acts by increasing the glucose reuptake by the body cells, it increases the storage of the glucose in the tissues as fats, and hence presenting with weight gain. In addition, it is administered as a daily dosage, and hence causing tissue damage due to frequent pricking. To counter the risk of hypoglycaemia, exenatide a glucagon-like receptor agonist is added into the therapy, to improve glycaemic control as well as eliminate the risk for hypoglycaemia and weight gain (Buse et al., 2011). All the same, it is very effective and very fast, and hence administered after measuring the blood glucose levels, and regulating the dosage according.

Exenatide, a glucagon-like peptide is recommended in the therapy with insulin and metformin to prevent weight gain. When administered as a subcutaneous injection, it has an added advantage since the new reconstitution is provided as one dose weekly, and has a better glycaemic control (Drucker et al., 2008). As a subcutaneous injection it has a high rate of absorption and bioavailability. It’s mechanism of action is blocking glucagon receptors, and hence increase insulin production. This increases the risk for hypoglycaemic in diabetic patients, in case they miss a meal or involve in a physical exercise that reduces the blood sugars.

In summary, gliclazide and metformin are oral drugs, with some beneficial effects such as bile acid metabolism and delays intestinal absorption of the glucose. Oral diabetogenics have slow rate of absorption and hence less likely to cause hypoglycaemia, except for gliclazide due to the high binding capacity. Basal insulin and exenatide are used as subcutaneous injections, causing tissue damage due to the frequent injections. Due to the high rate of absorption secondary to the method of administration, patients are more likely to go to hypoglycaemia at a higher rate. However, these drugs are fast acting, and hence can be used to drop very high sugars and prevent complications. In addition, exenatide is used with insulin to counter the weight gain effects of insulin, and hence safe for cardiac protection in obese patients.

Monitoring requirements and counselling points

There is need to keep record of the patient’s weight and basal mass index records. It is necessary to educate the patient on the benefits of daily weight measurement and waist circumference measurement (Koning, et al., 2007), to assess the risks for a cardiovascular disease. Any noted weight gain can therefore be noted early and acted upon accordingly. In addition, the patient should engage in exercises and walking or jogging to lose weight and hence reduce the basal mass index towards normal ranges (American Diabetes Association., 2006). This reduces further the chances of cardiovascular diseases and also helps to reduce the blood sugar levels (Lorber, 2014).

Dietary advice and monitoring is also necessary (Derosa et al., 2014). Eating a healthy, balanced diet is also necessary in teaching the type 2 diabetic patients. They should be encouraged to take foods rich in fibre and low glycaemic index foods which include fruits, vegetables, whole grains and pulses (Burger et al., 2012). The patient should also ensure low fat dairy products, and avoid oily fish. Discourage the use of processed carbohydrates such as cakes, but rather use the natural unprocessed sources of carbohydrates. The unprocessed carbs release the glucose in low amounts slowly, unlike the processed carbs.

Patient A also needs to be trained on drug administration, and sensitization on the benefits on compliance to the regimen provided. On introduction to insulin, it is necessary to train the patient on cool storage of the formulation, and the method of subcutaneous injection, as well as the sites applicable (Neumiller & To, 2011). The patient should be informed on the need to use one needle a time, rotate the site of injection and avoid repeating the injection on the same point. The patient should also be trained on monitoring blood glucose levels, and responding to the levels recorded accordingly.

In a nutshell, American and European guidelines recommend on diet modification and monitoring, exercise and workouts, weight monitoring and loss for the overweight and consistent clinical follow up via a clinic for the diabetic patients (American Diabetes Association., 2011). The patient needs to check on his diet to reduce high-energy foods and processed carbohydrates. Physical exercises help in loss of excess weights and reuptake of glucose in the blood into the tissues hence reduce blood sugar levels. Weight monitoring is necessary to prevent against obesity which predisposes to cardiovascular diseases.

References

American Diabetes Association. 2006. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care, 29(8), pp. 1963-1972.

American Diabetes Association. 2011. Standards of medical care in diabetes. Diabetes Care, 34(1), pp. 11-61.

Bunck, M.C., Diamant, M., Corner, A, et al. 2009. One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care, 32(5), pp. 762-8.

Burger, K.N., Beulens, J.W., van der Schouw, Y.T, et al. 2012. Dietary fiber, carbohydrate quality and quantity, and mortality risk of individuals with diabetes mellitus. PLoS One., 7: e43127.

Buse, J.B., Bergenstal, R.M., Glass, L.C., Heilmann, C.R., Lewis, M.S., Kwan, A.Y, et al. 2011. Use of twice-daily exenatide in Basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial. Ann Intern Med., 154(2), pp. 103-12.

Derosa, G., Limas, C.P., Macías, P.C., Estrella, A., Maffioli, P. 2014. Dietary and nutraceutical approach to type 2 diabetes. Arch Med Sci., 10, pp. 336-44.

Drucker DJ, Buse JB, Taylor K, Kendall DM, et al. “Exenatide once weekly versus twice daily for the treatment of type 2 diabetes”. A randomised, open-label, non-inferiority study. Lancet. 2008 Oct 4. 372(9645):1240-50.

Graham, G.G., Punt, J., Arora, M., et al. 2011. Clinical pharmacokinetics of metformin. Clin Pharmacokinetics, 50, pp. 81-98.

Inzucchi, S.E., Bergenstal, R.M., Buse, J.B., et al. 2015. Management of hyperglycemia in type 2 diabetes, 2015: a patient‐centered approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 38, pp. 140-149.

Koning, D. L., Merchant, A.T., Pogue, J., et al. 2007. Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: Meta-regression analysis of prospective studies. Eur Heart J., 28(7), pp. 850-6.

Lorber, D.  2014. Importance of cardiovascular disease risk management in patients with type 2 diabetes mellitus. Diabetes Metab Syndr Obes., pp. 169-83.

Neumiller, J.J., & To, S., 2011. Treating Type 2 Diabetes. Retrieved from https://www.diabetesselfmanagement.com/managing-diabetes/treatment-approaches/updated-treatment-guidelines-for-type-2-diabetes/  [Accessed 22 January 2019]

Rafieian-Kopaei, M., & Nasri, H. 2012. Ginger and diabetic nephropathy. J Ren Inj Prev.,  2, pp. 9-10.

Scarpello, J.H., & Howlett, H.C.  2008. Metformin therapy and clinical uses. Diabetes Vascular Disease Res., 5(3), pp. 157-167.

Xu, T., Brandmaier, S., Messias, A.C, et al. 2015. Effects of metformin on metabolite profiles and LDL cholesterol in patients with type 2 diabetes. Diabetes Care, 38(10), pp. 1858-1867.

Zhou, L., Liu, H., Wen, X., Peng, Y., et al. 2017. Effects of metformin on blood pressure in nondiabetic patients. A meta-analysis of randomized controlled trials. J Hypertens., 35(1), pp. 18-26.