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A person with diabetes that has a hypoglycemic reaction (low blood sugar) must ingest carbohydrate to reverse it.

Glucose tablets, each containing 4 grams of glucose, are certainly the most practical way of carrying carbohydrates. It is required to take 4 tablets in presence of a reaction, retest 15 minutes later, and retreat if the blood glucose level remains below 4 mmol/L.

However, glucose tablets, sold in drug stores, are quite expensive. It would be cheaper to carry sugar cubes (3 grams per cube) in a specially designed container, but this approach has never actually been tested to make sure that sugar cubes are efficacious. All the studies ahve been done with sugar diluted in water...

In our trial, we treated people having a hypoglycemia at the time of their routine visit at the Royal Victoria Hospital Metabolic Day Centre with either 4 tablets of glucose or with 5 sugar cubes. We wanted to test that these two approaches are equivalent. The results are being analyzed.

If they are, especially designed containers carrying 5 sugar cubes could be developed and provided to people with diabetes, providing a less expensive approach to treat hypoglycemic reactions.


The REWIND trial, sponsored by Eli Lilly, evaluates whether dulaglutide, administered by a once-weekly injection, can prevent the appearance of cardiovascular complications in people with type 2 diabetes.

This medication is known to improve diabetes control, while frequently causing weight loss.

9600 participate in this close to 7 year study.


The EXSCEL trial sponsored by AstraZeneca, assesses if the drug Exenatide QW, administered by a weekly injection, can prevent the appearance of cardiovascular complications in people with type 2 diabetes.

This medication is known to improve glucose control, while causing weight loss. This medication is already on the market in the United States.9500 people participate in this study, which is expected to last 6 years.


The Opt2mise trial, sponsored by Medtronic, assessed the use of an insulin pump in people with type 2 diabetes.

The use of an insulin pump is widespread in type 1 diabetes, but has been less studied in type 2 diabetes.

In this trial, it was shown that the use of an insulin pump in patients with type 2 diabetes who were poorly controlled on multiple daily injections of insulin improved more their diabetes control than continuing on the multiple daily injections.

Reznik Y, Cohen O, Aronson R, Conget I, Runzis S, Castaneda J, Lee SW; OpT2mise Study Group.Insulin pump treatment compared with multiple daily injections for treatment of type 2 diabetes (OpT2mise): a randomised open-label controlled trial.
Lancet. 2014 Oct 4;384(9950):1265-72. doi: 10.1016/S0140-6736(14)61037-0. Epub 2014 Jul 2


The TECOS trial, sponsored by Merck, assessed whether sitagliptin use in type 2 diabetes had beneficial or deleterious cardiovascular effects in the long term.

14000 people participated in this trial. The results are expected to be made public in June 2015.


The SAVOR-TIMI trial, sponsored by Bristol Myers Squibb and AstraZeneca,assessed whether saxagliptin, an anti-diabetes drug, was safe and whether it could prevent the appearance of cardiovascular complications in people with type 2 diabetes.

16500 people participated in this 5 year trial. The trial revealed that saxagliptin therapy was safe on the cardiovascular aspect. There was no reduction in cardiovascular effects, and a small increase in the cases of heart failure with saxagliptin therapy.

Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I, SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 369(14) :1317-26, 2013


The ACCORDION trial assessed in the long term the patients that participated in the ACCORD trial (see other page), without any further intervention.

The objective of this trial was to see if intensive glucose control, intensive blood pressure control or the use of fenofibrate added to a statin would have positive or negative effects in the long term that may not have been noticed at the end of the ACCORD trial.

The data are being analyzed.


The ORIGINALE trial is a long-term follow-up of those that participated in theORIGIN trial (see other page).

The objective of this trial was to assess if the early treatment with Glargine insulin (early after diagnosis of type 2 diabetes or even before diagnosis) could have beneficial or deleterious effects that would not have been detected at the end of the ORIGIN trial.

The data are being analyzed.


10,000 people participated in this trial, including 120 at the Royal Victoria Hospital

Is there an advantage to obtain a strict glucose control with an A1c below 6%?
In the group that achieved an A1c of 6.4% (glucose levels before meals under 6...), there was a reduction in the microvascular complications (eyes, nerves and kidneys). There was also a 24% reduction in myocardial infarcts. However, total and cardiovascular mortality were increased in that group. This increase is not explained at present. Those that were able to achieve an A1c under 6.5% did not have this increased mortality. It seems it is those that were unable to reduce their A1c despite being in the intensive group that had the highest mortality, and those that had the greatest number of hypoglycemic reactions. Our interpretation is that some people are unable to reduce their A1c without having numerous hypoglycemic episodes that may be dangerous for the heart (arrhythmias).

Is there an advantage to reduce the systolic blood pressure to less than 120 (compared to less than 140) ?
The ACCORD trial showed a small decrease in strokes, but more side effects. There was no improvement in the other cardiovascular outcomes such as myocardila infarcts. The goal in people with diabetes therefore remains at 130/80 or less.

Is there an advantage to give fenofibrate (Lipidil) in addition to statins (Zocor, Lipitor, Crestor) ?
The ACCORD trial showed no benefit of adding fenofibrate for the cardiovascular outcomes, but showed a 40% reduction in the progression of diabetic eye disease (retinopathy)

Can severe hypoglycemia lead to dementia ?
The ACCORD trial suggested this is not the case. However, when people develop dementia such as when they have Alzheimer's disease, they become much more susceptible to severe hypoglycemia.

The ACCORD Study Group, Gerstein HC, Miller ME, Genuth S, Ismail-Beigi F, Buse JB, Goff DC Jr, Probstfield JL, Cushman WC, Ginsberg HN, Bigger JT, Grimm RH Jr, Byington RP, Rosenberg YD, Friedewald WT. Long-Term Effects of Intensive Glucose Lowering on Cardiovascular Outcomes. N. Engl. J. Med 364: 818-28, 2011


The INSIGHT trial compared the traditional approach in type 2 diabetes (addingone, then two, then three oral agents before initiating insulin) and an earlier insulin therapy. The trial showed better glycemic control when insulin was started early, but with more mild hypoglycemia and weight gain. Questionnaires revealed a better quality of life.

This study therefore suggests insulin may be an alternative early in diabetes management. However, it is probable that insulin will remain a used mostly when other therapies fail.

The main contribution of this study however was to validate a simplified approach to insulin initiation. This approach (the INSIGHT protocol) is based on patient-driven adjustments at home without the need of any calculation. The starting dose is 10 units, and the patients increase their dose by 1 unit every night until their glucose level before breakfast is under 5.5.

Reference :
Gerstein H, Harris S, Yale JF, Stewart J, Dempsey E. A randomized trial of adding insulin glargine vs avoidance of insulin in people with type 2 diabetes on either no oral glucose-lowering agents or submaximal doses of metformin or sulphonylureas. The Canadian INSIGHT study. Diabetic Med. Jul;23(7):736-42, 2006.


The START trial assessed a simple approach of intensifying insulin therapy when a single injection of basal insulin at bedtime with or without oral agents is insufficient to control glucose levels.

In this trial, the subjects with poor control on one injection of basal insulin first had their dose of basal insulin optimized by increasing the dose until the morning glucose was under 6. Other subjects with poor glucose control on oral agents alone were started on basal insulin, which was adjusted until the morning glucose levels were under 6.

Those that reached glucose levels of 6 or less with basal insulin, but with A1c levels above 7 (therefore glucose levels too high the rest of the day) then started rapid-acting analogue insulin before breakfast. The trial randomly divided the subjects in 2 groups: 1 group of patients adjusted their insulin dose by themselves, starting at 2 units and increasing by 1 unit every day until a glucose level two hours after breakfast was under 8, while the other group had the help of health professionals to make the adjustments. The trial showed that the simplified approach by patients was as effective.

Harris SB, Yale JF, Berard L, Stewart J, Abbaszadeh B, Webster-Bogaert S and Gerstein HC. Does a patient-managed insulin intensification strategy with insulin glargine and insulin glulisine provide similar glycemic control as a physician-managed strategy? Results of the START (Self-titration with Apidra to Reach Target) Study - A randomized non-inferiority trial. Diabetes Care 2014 Mar 37(3) :604-10. Doi 10.2337/dc13-1636. Epub 2013 Oct 29


The SOLVE trial observed the evolution of 17374 people with type 2 diabetes when basal insulin (detemir) was initiated to help better control their diabetes.

The trial occurred in 10 countries, and also assessed the differences between countries.

The trial first demonstrated the efficacy and safety of initiating basal insulin, with an average 1% reduction in A1c without any weight gain and with very little hypoglycemic episodes. There was actually a small weight loss in average, and less hypoglycemic episodes than when on oral agents alone.

The trial then showed that the teaching required to initiate insulin therapy lasted 40 minutes in average.

Finally, the study documented that physicians wait too long before initiating insulin, the average A1c at insulin initiation being 9%.

Khunti K, Caputo S, Damci T, Dzida GJ, Ji, Kaiser M, Karnielli E, Liebl A, Ligthelm R, Nazeri A, Orozco-Beltran D, Pan C, Ross S, Svendsen AL, Vora J, Yale JF, Meneghini L on behalf of the SOLVE Study Group: The Safety and Efficacy of Adding Once-daily Insulin Detemir to Oral Hypoglycaemic Agents in Patients with Type 2 Diabetes in a Clinical Practice Setting in Ten Countries. Diabetes, Obesity and Metabolism 2012 2012 Jul 25 (doi : 10.1111/j.1463-1326.2012.01665.x EPub ahead of print


The DREAM trial assessed whether the use of rosiglitazone in people with pre-diabetes could prevent the onset of type 2 diabetes.

Rosiglitazone reduced the appearance of diabetes by 60% over 3 years, which is the most powerful preventive approached described yet.

Unfortunately, this trial also raised doubts about the safety of rosiglitazone: increase in fractures after 3 years, particularly in women, and a possible increase in myocardial infarcts.

This medication is therefore not recommended for the prevention of diabetes.

The DREAM Trial Investigators. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. Sep 23;368(9541):1096-105, 2006.

DIA3004 Trial

This trial assessed the use of an SGLT2 inhibitor, canagliflozin, in people withdiabetes with moderate renal failure.

The study revealed that canagliflozin remained effective in presence of moderate renal failure, with A1c reductions of 0.4% and a 1.5 Kg weight loss over 6 months. There was a systolic blood pressure reduction of 6 mm Hg. There was an increase in symptoms compatible with hypotension, and rare hyperkalemia.

Reference :
Yale JF, Bakris G, Cariou B, Yue D, David-Neto E, Xi L, Figueroa K, Wajs E, Usiskin K, Meininger G. Efficacy and Safety of Canagliflozin in Subjects with Type 2 Diabetes and Chronic Kidney Disease). Diabetes, Obesity & Metabolism, 15 :463-73, 2013


The ORIGIN trial assessed the early use of basal insulin (Glargine) either atdiabetes onset or even before diabetes onset, compared with the traditional approach consisting of using up to 3-4 kinds of oral agents before initiating insulin.

12612 people participated during 6 years in average.

The use of a single daily dose of glargine insulin resulted in a spectacular glucose control, significantly better than the traditional approach, with a small weight increase and some hypoglycemic reactions, usually mild.

Glargine insulin had no effects, neither positive nor negative, on the occurrence of cardiovascular outcomes and cancers.

ORIGIN Trial Investigators, Gerstein HC, Bosch J, Dagenais GR, Diaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Ryden LE, Yusuf S. Basal insulin and cardiovascular and other outcomes in dysglycemia. N.E.J.M. 367(4) : 319-28, 2012