Case study: Adult with uncontrolled type 2 diabetes of 3 years duration Authored by Pablo Aschner and Linong Ji on behalf of the Global Partnership for Effective Diabetes Management. The Global Partnership for Effective Diabetes Management is supported by an unrestricted educational grant from Bristol-Myers Squibb, AstraZeneca LP.
This case study outlines the treatment of an adult who was diagnosed with type 2 diabetes 3 years ago and has uncontrolled hyperglycaemia (HbA 1c 9%; 75 mmol/mol) The case reflects a full range of treatment and management tools available in the European/US context* *The management of any patient is subject to social, economic, gender, age, co-morbidity and ethnic variables, and is dependent on the range of treatment options available in specific regions or countries.
Patient history and current medication use John, 56 years old, lives with his wife He works as a used car salesman, which involves long hours John was diagnosed with type 2 diabetes 3 years ago; since then, he has lost 7 kg (15.4 lbs) John s control of his diabetes fluctuates and his blood glucose levels have risen gradually Coinciding with this, he underwent upward titrations of metformin to try to establish glycaemic control 12 months ago John was also prescribed a DPP-4 inhibitor as a result of further serious deteriorations in blood glycaemic control Current medication Metformin 1000 mg b.i.d. Sitagliptin 100 mg o.d. Valsartan 200 mg o.d. b.i.d., twice daily; o.d., once daily.
Current status/biochemistry Previous visit (1 month ago) FPG: 13.7 mmol/l HbA 1c : 9.1% LDL-cholesterol: 1.2 mmol/l HDL-cholesterol: 1.6 mmol/l Triglycerides: 1.3 mmol/l Blood pressure: 126/78 mmhg BMI: 27.7 kg/m 2 Current visit FPG: 14.1 mmol/l HbA 1c : 9.3% LDL-cholesterol: 1.1 mmol/l HDL-cholesterol: 1.5 mmol/l Triglycerides: 1.2 mmol/l Blood pressure: 124/77 mmhg BMI: 27.5 kg/m 2 At John s previous visit, his HbA 1c was substantially above his target range of 6.5 7.0% and has risen further. The doctor reminded John about the importance of sticking rigidly to diet and exercise interventions and taking his medication as prescribed. He also suggested they needed to revise John s therapy. Click here to change units BMI, body mass index; FPG, fasting plasma glucose; HbA 1c, glycosylated haemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein.
Current status/biochemistry Previous visit (1 month ago) FPG: 247 mg/dl HbA 1c : 76 mmol/mol LDL-cholesterol: 46 mg/dl HDL-cholesterol: 62 mg/dl Triglycerides: 115 mg/dl Blood pressure: 126/78 mmhg BMI: 27.7 kg/m 2 Current visit FPG: 254 mg/dl HbA 1c : 78 mmol/mol LDL-cholesterol: 43 mg/dl HDL-cholesterol: 58 mg/dl Triglycerides: 106 mg/dl Blood pressure: 124/77 mmhg BMI: 27.5 kg/m 2 At John s previous visit, his HbA 1c was substantially above his target range of 48 53 mmol/mol. The doctor reminded John about the importance of sticking rigidly to diet and exercise interventions and taking his medication as prescribed. He also suggested they needed to revise John s therapy. Click here to change units BMI, body mass index; FPG, fasting plasma glucose; HbA 1c, glycosylated haemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein.
Response to poor control Question What is an appropriate response to John s lack of glycaemic control? Ask John to return for reassessment in 1 month Explore the reasons for poor glycaemic control Intensify antihyperglycaemic therapy
Response to poor control Question What is an appropriate response to John s lack of glycaemic control? Ask John to return for reassessment in 1 month Explore the reasons for poor glycaemic control Intensify antihyperglycaemic therapy John s blood glucose levels are already uncontrolled; this places John at risk of a range of vascular complications As such, extended periods of uncontrolled hyperglycaemia should be avoided 1 Achieving glycaemic control requires careful assessment of the potential reasons for poor disease management 1 If poor adherence is not suspected, medication should be altered without delay in order to provide adequate control 1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765.
Physician-patient discussion The doctor explains the dangers of extended periods of uncontrolled hyperglycaemia. He asks John: If he is adhering to lifestyle interventions and medication To explain his medication regimen Whether he is experiencing any side-effects of therapy If he has any concerns regarding the use of his medication How well he feels he is coping with his diabetes John reports: Good adherence to lifestyle interventions: he tries to be active and eats healthily most of the time That he always takes his medication Mild GI discomfort on occasion, but otherwise no side-effects Generally feels well, and has no major concerns, but is often tired A positive attitude towards his condition GI, gastrointestinal.
Glycaemic target Glycaemic targets should always be individualized, based on a range of factors The doctor and John discuss his target for glycaemic control Question What is the most appropriate glycaemic target * for John? <6.0% 6.0 6.5% 6.5 7.0% 7.0 7.5% 7.5 8.0% 8.0 8.5% *Equivalent values: 6.0% = 42 mmol/mol; 6.5% = 48 mmol/mol; 7.0% = 53 mmol/mol; 7.5% = 58 mmol/mol; 8.0% = 64 mmol/mol; 8.5% = 69 mmol/mol.
Glycaemic target What is the most appropriate glycaemic target * for John? <6.0% 6.0 6.5% 6.5 7.0% 7.0 7.5% 7.5 8.0% 8.0 8.5% Long periods of uncontrolled hyperglycaemia increase John s risk of vascular complications A near normal glycaemic target (HbA 1c 6.5 7.0%) is appropriate for those with inadequate glycaemic control and no complications, if it can be achieved safely and without delay 1 Other factors favouring a more stringent target include John s age and long potential life expectancy, absence of comorbidities and positive attitude 2 A glycaemic target of 6.0 6.5% is generally reserved for those with newly diagnosed disease and no complications 1,2 *Equivalent values: 6.0% = 42 mmol/mol; 6.5% = 48 mmol/mol; 7.0% = 53 mmol/mol; 7.5% = 58 mmol/mol; 8.0% = 64 mmol/mol; 8.5% = 69 mmol/mol. 1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765. 2. Inzucchi S E et al. Diabetes Care 2012;35:1364 1379.
Achieving glycaemic control The doctor does not feel that poor adherence is the reason for John s lack of glycaemic control He explains to John that his medication requires adjustment in order to restore control of his blood glucose levels He reiterates that continued adherence to diet and exercise interventions is essential if John is to achieve glycaemic control Question Alongside lifestyle interventions, what is an appropriate choice of antihyperglycaemic medication for John? Add a sulphonylurea Add pioglitazone Add basal insulin Add a GLP 1-receptor agonist
Option selected: Add a sulphonylurea When glycaemic control is no longer being achieved with dual therapy, progression to triple oral therapy may offer some benefit 1 Sulphonylureas have good glucose lowering efficacy, but are associated with a moderate risk of hypoglycaemia 1,2 Sulphonylureas may also cause weight gain 1,2 In addition, when two oral therapies are no longer providing sufficient control, adding a third oral agent is likely to decrease HbA 1c by 1.5%, which will be insufficient to reach John s glycaemic target 3,4 Sulphonylurea 1,2 HbA 1c efficacy: High Hypoglycaemia risk: Moderate Weight effect: Gain Major side effects: Hypoglycaemia Cost: Low 1. Inzucchi SE et al. Diabetes Care 2012;35:1364 1379. 2. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765. 3. Rosenstock, J et al. Diabetes Care 2006;29:554 559. 4. Roberts, VL. Clin Ther 2005;27:1535-47. Please select another option
Option selected: Add pioglitazone When glycaemic control is no longer being achieved with dual therapy, progression to triple oral therapy may offer some benefit 1 Pioglitazone has a low risk of hypoglycaemia; however, it causes weight gain and is associated with an increased risk of fluid retention, heart failure 1,2 and fracture 3 In addition, when two oral therapies are no longer providing sufficient control, adding a third oral agent is likely to decrease HbA 1c by 1.5%, which will be insufficient to reach John s glycaemic target 4,5 Pioglitazone 1,2 HbA 1c efficacy: Intermediate Hypoglycaemia risk: Low Weight effect: Gain Major side effects: Fluid retention Cost: High 1. Inzucchi SE et al. Diabetes Care 2012;35:1364 1379. 2. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765. 3. Dortmuth CR et al. Arch Intern Med 2009;169:1395 1402. 4. Rosenstock, J et al. Diabetes Care;2006;29:554 559. 5. Roberts, VL. Clin Ther. 2005;27:1535-47. Please select another option
Option selected: Add a GLP-1 receptor agonist When glycaemic control is no longer being achieved with dual therapy, adding a third non-insulin agent may offer some benefit 1 Advantages of GLP-1 receptor agonists: 1,2 Associated with weight loss Can lower HbA 1c by as much as basal insulin when HbA 1c is <10% 3 However, they are often associated with initial GI discomfort and clinical experience with these agents is currently limited 1,2 GLP-1 agonist 1,2 HbA 1c efficacy: High Hypoglycaemia risk: Low Weight effect: Neutral/loss Major side effects: GI Cost: Moderate GI, gastrointestinal; GLP, glucagon-like protein. 1. Inzucchi SE et al. Diabetes Care 2012;35:1364 1379. 2. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765. 3. Hall, GC et al. Diabet Med 2013;30,681 686. Please select another option
Option selected: Add basal insulin When glycaemic control is no longer being Insulin achieved with dual therapy, adding a third 1,2 non-insulin agent may offer some benefit 1 HbA 1c efficacy: Highest However, when two oral therapies are no Hypoglycaemia risk: High longer providing sufficient control, the most Weight effect: Gain robust response will usually be with insulin 1,2 Major side effects: Hypoglycaemia Disadvantages of insulin include high risk of hypoglycaemia and weight gain 1,3 Cost: Variable The doctor explains that hypoglycaemic risk can be minimized through SMBG Metformin in combination with insulin may counteract any weight gain and has apparent CV benefits 1,2 By enhancing the residual endogenous insulin response to meals, DPP-4 inhibitors may also confer benefits when used in combination with basal insulin and metformin DPP-4 inhibitors are also weight neutral John is reluctant, but agrees to give this combination a try CV, cardiovascular; DPP, dipeptidyl peptidase; SMBG, self-monitoring of blood glucose. 1. Inzucchi SE et al. Diabetes Care 2012;35:1364 1379. 2. Rosenstock, J et al. Diabetes Care 2006;29:554 559. 3. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765.
Percentage reduction in event rate Glargine and detemir are long-acting basal insulin analogues; these are often preferred over NPH insulin due to: 1 Longer duration of action (particularly glargine) Less pronounced peak in time-action profiles More consistent effects Decreased risk of hypoglycaemia 2 NPH insulin shows a distinctive peak in time-action profiles, 3 which can increase risk of hypoglycaemia. Risk can be minimized by administering before bedtime The doctor and John decide to use glargine o.d. before bedtime to achieve glycaemic control 2 Choice of insulin Percentage reduction in hypoglycaemic event rates with insulin glargine versus NPH insulin 2 60 Symptomatic events * 50 Confirmed events Severe events 40 * 1. Poon K and King AB. Drug Healthc Patient Saf 2010;2:213 223. 2. Mullins P et al. Clin Ther 2007;29:1607 1619. 3. Owens DR et al. Diabetes Care 2000;23:813 819. NPH, neutral protamine Hagedorn. 30 20 10 0 * * Type 1 diabetes * Type 2 diabetes Data are from 5 (type 1) and 6 (type 2) phase III or IV diabetes trials. Symptomatic = all symptomatic events; confirmed = symptomatic events with a confirmatory glucose level of 3.6 mmol/l (65 mg/dl) or plasma glucose of <3.2 mmol/l (58 mg/dl); severe = symptomatic events requiring treatment assistance from a third party. *p<0.05 compared with NPH insulin.
Preventing and managing hypoglycaemia SMBG is an essential component of diabetes management in patients using insulin It is used to adjust medication in response to fluctuations in blood glucose levels, helping to reduce the risk of hypoglycaemic and hyperglycaemic events The doctor advised John to maintain his FPG between 3.9 and 7.2 mmol/l (70 130 mg/dl), 2 and referred him to a specialist diabetes nurse to learn about SMBG, how to adjust insulin dose according to SMBG and how to recognize and respond to hypoglycaemia/hyperglycaemia If John becomes hypoglycaemic and feels able to self treat, he is advised to: Ingest 15 g of glucose or sucrose, wait 15 minutes then take another 15 g glucose/sucrose if BG is <4.0 mmol/l (click i, below, for examples) Have a meal or snack to prevent recurrence once hypoglycaemia is reversed In cases of severe hypoglycaemia, where John requires assistance to treat: 20 g of glucose/sucrose should be given in the first instance to a conscious person 1,2 For an unconscious individual, glucagon may be administered by a friend/caregiver; the emergency services should also be called 1,2 Show examples of 15 g glucose/sucrose 1. Canadian Diabetes Association. Can J Diabetes 2008;32:S20 S201. 2. American Diabetes Association. Diabetes Care 2013;36:S11 S66. FPG, fasting plasma glucose; SMBG, self-monitoring of blood glucose.
Preventing and managing hypoglycaemia SMBG is an essential component of diabetes management in patients using insulin It is used to adjust medication in response to fluctuations in blood glucose levels, helping to reduce the risk of hypoglycaemic and hyperglycaemic events The doctor advised John to maintain his FPG between 3.9 and 7.2 mmol/l (70 130 mg/dl), 2 and referred him to a specialist diabetes nurse to learn about SMBG, how to adjust insulin dose according to SMBG and how to recognize and respond to hypoglycaemia/hyperglycaemia If John becomes hypoglycaemic and feels able to self treat, he is advised to: Ingest 15 g of glucose/sucrose, wait 15 minutes then take another 15 g glucose/sucrose if BG is <4.0 mmol/l (click i, below, for examples) Examples of 15 g of glucose/sucrose for treatment of mild Have a meal or snack to prevent recurrence once hypoglycaemia is reversed to moderate hypoglycaemia In cases of severe hypoglycaemia, where John requires assistance to treat: 2015 g g of of glucose/sucrose in the form should of glucose be given tablets in the first instance to a conscious person 15 ml 1,2 (3 teaspoons) of table sugar dissolved in water For 175 an ml unconscious (3/4 cup) of individual, juice or regular glucagon soft may drink be administered by a friend/caregiver; 15 ml (3 teaspoons) the emergency of honey services should also be called 1,2 Hide examples of 15 g glucose/sucrose 1. Canadian Diabetes Association. Can J Diabetes 2008;32:S20:S201. 2. American Diabetes Association. Diabetes Care 2013;36:S11 S66. FPG, fasting plasma glucose; SMBG, self-monitoring of blood glucose.
3 month follow-up During the past 3 months John has been adjusting his insulin dose (with the help of the nurse) to counteract fluctuations in his blood glucose levels He has responded well to therapy and his HbA 1c is beginning to decrease towards the target level He says self monitoring can sometimes be a bit of a nuisance but nonetheless he maintains good records in his diary John has experienced minimal weight gain (2 kg; 4.4 lbs) The doctor continues to emphasize the importance of adherence to diet and exercise interventions and medication in order to achieve his target blood glucose level Current status FPG: HbA 1c : BP: 7.0 mmol/l (126 mg/dl) 7.5% (58 mmol/mol) 125/78 mmhg BMI: 28.1 kg/m 2 BMI, body mass index; BP, blood pressure; FPG, fasting plasma glucose; HbA 1c, glycosylated haemoglobin.
10 Steps to get more type 2 diabetes patients to goal The Global Partnership for Effective Diabetes Management recommends: 1 10 Steps to get more people with type 2 diabetes to goal: Aim for an appropriate individualized glycaemic target, e.g. HbA 1c 6.5 7% (48 53 mmol/mol) (or fasting/preprandial plasma glucose 110 130 mg/dl [6.0 7.2 mmol/l] where assessment of HbA 1c is not possible) when safe and appropriate. Monitor HbA 1c every 3 months in addition to appropriate glucose self-monitoring. Appropriately manage all cardiovascular risk factors. Refer all newly diagnosed patients to a unit specializing in diabetes care where possible. Address the underlying pathophysiology of diabetes, including the treatment of β-cell dysfunction and insulin resistance. Treat to achieve appropriate target HbA 1c within 6 months of diagnosis. After 3 months, if patients are not at the desired target HbA 1c, consider combination therapy. Consider initiating combination therapy or insulin for patients with HbA 1c 9% ( 75 mmol/mol). Use combinations of antihyperglycaemic agents with complementary mechanisms of action. Implement a multidisciplinary team approach that encourages patient self-management, education and self-care, with shared responsibilities to achieve goals. HbA 1c, glycosylated haemoglobin. 1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765.
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