The complexity of managing T2D – a GP’s perspective

13th November 2019, Drs Chee Khoo & Sobhy Khalil

We have a contribution from our GP colleague this week. Dr Sobhy Hakeem KHALIL who thoroughly studied the ADA/EASD Management of Hyperglycaemia In Type 2 Diabetes, 2018 Consensus Report and provided his take on the guidelines. I have added my comments to his take (in blue):

  1. They emphasised the importance of life style changes such as weight reduction, physical activities (aerobic and high resistance activities) and smoking cessation.
  2. Good glycaemic management both improve symptoms and long-term outcome, however while impact on microvascular complications is clear, impact on macro vascular complications is less clear. It is clear for heart failure though, which is the new kid on the block. It’s not related to coronary arteries but to the myocytes. Macrovascular benefits are there but not evident till >10 years but hearty failure is definitely related to glycaemic control.
  3. Medical Nutrition Therapy, along with life style changes cited above, along with psychological support delivered in the context of Diabetes Self-Management, Education and Support DSMES are fundamental to Diabetes Care
  4. Multiplicity of available agents offer some benefits but can complicate choice of agent. The difficulty with the choice is actually simpler with the new EASD/ADA 2018 guidelines but made more complicated because of PBS restrictions. You can see from the slides on the weekend that one need to take into consideration a whole host of other factors apart from glucose reduction potency when considering escalation of treatment
  5. Target HbA1c should be individualized, but generally 7 % or less for an adult with a normal life expectancy. Comorbid conditions and frailty would indicate a more modest target.
  6. Controlling modifiable risk factors in patients with ASCVD with diabetes, conferred significant benefits.
  7. HbA1c is an excellent measurement of glycaemic control, but fallacies arise from ; anaemia , haemoglobinopathy, ESRF, ethnicity and pregnancy.  Self monitored blood glucose (SMBG) in Type 2 diabetes, confers some benefits which are considered to be limited. HbA1c is also not reliable in situations where there is possibility of hypoglycaemia. The HbA1c reading can be diluted by the presence of hypoglycaemia.You will recall how useful SMBG was in our sessions. The studies that conclude that it doesn’t help were flawed because they were not structured SMBG and there were no physician supervision. Patients doing SMBG on their own leads nowhere.
  8. Following knowledge of the above item DSMES should be appropriately delivered. So: Assess and Teach + Give written materials. Support ongoing management – person & family, Teach what is diabetes, aim and methods of treatment and complications that need detection à monitor progress and success of DSMES. This intervention has improved glycaemic control and reduced hospitalization and mortality.
  9. Adherence barriers should be identified in the individual patient and a change of regimen, education, facilitation and other factors are addressed to enhance adherence to treatment.
  10. Recent studies established recommendation of early use of SGLT2i & GLP1-RA in CVD & CKD, as they have proven cardiovascular benefits.
  11. Of the GLP1-RAs, the most favourable was Liraglutide followed by Semaglutide. Exenatide and Lixisenatide showed no CVD benefit but CV harm.
  12. SGLT2i use showed significant CVD benefits, best being Empagliflozin which was more beneficial than Canagliflozin. SGLT2i are beneficial in HF patients but GLP1-RAs were not. As more studies come in, it would appear that the CVD benefits are really heart failure benefits and all the SGLT2 inhibitors appear similar with none able to claim superiority over the other. The reasons for the different results in the different studies are due to the different design of the study, different primary outcomes and different patient cohorts. Canagliflozin is used extensively in US but is no longer available in Australia. We have Empagliflozin, Dapagliflozin and Ertugliflozin.
  13. DPP4i have no CV benefit or risk except for Saxagliptin which was shown to increase hospitalisation for HF.
  14. In patients with CKD, use SGLT2i to reduce progression but if contraindicated, use GLP1-RA.
  15. Diet approaches can include Mediterranean diet, meal replacement, vegetarian diet, energy restriction with counselling, and low Carbohydrate diet. Physical activities can include; running, cycling, walking, swimming and others. Add resistance exercises to that.
  16. Metformin is the first choice pharmacological intervention in T2D. Doses of 3000 mg are used in some places but doses above 2000 mg are unlikely to add more benefit. It should not be used once eGFR has reached 30 ml/min or less and during acute illness, vomiting and dehydration it should be withheld. Some titration is required if the eGFR is <60 ml/min.
  17. SGLT2i: Empagliflozin, Canagliflozin, Dapagliflozin and Ertugliflozin are effective in all disease stages and they decrease weight, BP, MACE, HF & CKD. NONE OF THE SGLT2i members have been approved for eGFR 45ml /min or less. They do not cause hypoglycaemia. They have some common side effects and rare but serious side effects such as increased risks of amputation, AKI, DKA, fractures and Fournier gangrene.
  18. GLP1-RA: All given by SC injection; Dulaglutide, Exenatide extended release and Semaglutide are given weekly, Liraglutide and Lixisenatide are given daily and a preparation of Exenatide is given twice daily. Nausea, vomiting and diarrhoea are the commonest side effects but these improve with time. Pancreatitis and pancreatic cancer do not represent a substantial risk, but gallbladder events do increase. Semaglutide increased retinopathy. The jury is not quite settled in this one as the numbers are very small. It is not uncommon for retinopathy to occur when HbA1c reduces too rapidly. So, it is probably not to do with the drug but the potency of the agent in reducing glucose.
  19. DPP4i: Saxagliptin, Alogliptin, Sitagliptin and Linagliptin . All except the latter need adjustment for renal function except Linagliptin . Weight neutral , well tolerated and does not cause hypoglycaemia . Increased HF hospitalisation was noted with Saxagliptin.  
  20. Sulphonylureas: Glibenclamide Glyburide, Glipizide , Gliclazide , Glimepride are cheap , effective and reduce macrovascular disease, but CV safety is uncertain and they may hasten secondary failure and may cause increased weight.
  21. TZD (Pioglitazone): low hypoglycaemic risk and may decreases Trig & ASCVD. However they cause fluid retention and HF, Bone loss and fractures, increase LDL (Rosiglitazone) and macular oedema.
  22. Insulins are highly effective and effect is directly proportional to the dose and come in so many preparations and devices. A good plan for those who are commencing insulin is to begin with a long acting (basal Insulin). While GLP1 receptor agonists are preferred to insulin, Insulin is recommended for those with symptomatic hyperglycaemia .
  23. Obesity management lines include; various forms of diet plans, increased physical exertion phentermine, Orlistat, various forms of metabolic surgery. Don’t forget Saxenda and the new Contrave, low calorie or very low-calorie diets.

MAJOR BARRIER FOR ME IN IMPLEMETING THE NEW GUIDELINES:

  1. Poor level of patient’s education interferes with grasping complicated concepts. Many of my patients are illiterate in English and even in their native language. Referral to a CDE to address some of these barriers.
  2. The energy, time and deliberations needed to implement the changes are difficult to afford by a solo practitioner. If I were to implement the guidelines fully, I need a diabetes educator / nurse  readily available to advise and educate my patients  and to instruct them on the nitty gritty day to day intricacies and injection techniques. Yes, everyone has the same problem but it is surprisingly not as time intensive as you think. Do that over a number of consultations. The number of patients with diabetes which require intensive work is actually not high and manageable over the course the year as was discussed at the meeting. Further, if you have a switched on and trained practice nurse, they can help in patient education. DOMTRU runs a practice nurse workshop once a year.
  3. I believe the following proposal would be very useful and fruitful, when community GPs are allowed to have paid training / attachment in diabetes clinics say one morning per week for a semester of 3 months. This hand on training is complementary to academic education like this one. Paying GPs to education is unlikely to ever take happen. DOMTRU has commenced a uniclinic at WSU whereby GPs can spend time to update their management skills. Let me know if that is of interest to you. Otherwise the case conference system allows you to learn about management in complicated cases.
  4. The wording of authority criteria for prescribing some anti-diabetic medication, occasionally stands in the way of prescribing what the guidelines recommend. PBS is always going to be out of sync with guidelines. Attending sessions like the Diabetes Injectable Workshop helps to demystifying those PBS restrictions.
  5. Faced with a patient who added weight since last review, with HbA1c of 8.5 %, the eternal question boils within me; Should I intensify pharmacological treatment or admonish patient to comply more genuinely to better diet and exercise. Don’t forget that these patients had been trying for many years with diet and exercise. What else will they do that is different? If you have patients who wants to give them another go, then setting a fixed time line is useful. “see you in 3 months let’s see how successful you can be and if you don’t get the numbers down, intensifying pharmacological treatment is then necessary. Or you can always tell patients that we do both and if the lifestyle issues is successful, we can always de-escalate treatment.
  6. Tailoring regimens to individual circumstances presents the following frustrating and often confusing scenarios; such as Mr A who is 87 years old with HbA1c of 9.5 % , Mrs B who is a refugee with osteoarthritis and unable to walk , Mr C who works as a truck driver and gets seen only minutes before closing hour asking for a script for his medications, when his last blood test was over 6 months previously. Yes, arranging a working recall system helps so that you can tie them over for the next month but arrange for patient to come back for review works. So, giving them 5 repeats means they will be back in 6 months. “No blood test results, no scripts”. Or do a non-fasting bloods. Only the triglycerides are dependent on the fasting state.
  7. I think the Government should consider Medicare rebate for bariatric surgery for all diabetic patients with BMI of 35 or over, as this is a hurdle to many suitable patients for this form of management.

Having said all the above, I believe I have learnt a lot from reading the predisposing activity and I will try to implement whatever I can of the recommendations.