Metformin, Sulfonylureas, or Other Antidiabetes Drugs and the Risk of Lactic Acidosis or Hypoglycemia

OBJECTIVE: Lactic acidosis has been associated with use of metformin. Hypoglycemia is a major concern using sulfonylureas. The aim of this study was to compare the risk of lactic acidosis and hypoglycemia among patients with type 2 diabetes using oral antidiabetes drugs. RESEARCH DESIGN AND METHODS: This study is a nested case-control analysis using the U.K.-based General Practice Research Database to identify patients with type 2 diabetes who used oral antidiabetes drugs. Within the study population, all incident cases of lactic acidosis and hypoglycemia were identified, and hypoglycemia case subjects were matched to up to four control patients based on age, sex, practice, and calendar time. RESULTS: Among the study population of 50,048 type 2 diabetic subjects, six cases of lactic acidosis during current use of oral antidiabetes drugs were identified, yielding a crude incidence rate of 3.3 cases per 100,000 person-years among metformin users and 4.8 cases per 100,000 person-years among users of sulfonylureas. Relevant comorbidities known as risk factors for lactic acidosis could be identified in all case subjects. A total of 2,025 case subjects with hypoglycemia and 7,278 matched control subjects were identified. Use of sulfonylureas was associated with a materially elevated risk of hypoglycemia. The adjusted odds ratio for current use of sulfonylureas was 2.79 (95% CI 2.23–3.50) compared with current metformin use. CONCLUSIONS: Lactic acidosis during current use of oral antidiabetes drugs was very rare and was associated with concurrent comorbidity. Hypoglycemic episodes were substantially more common among sulfonylurea users than among users of metformin.Merck SA, Lyon, Franc

Further Insights into the Catalytic Reduction of Aliphatic Polyesters to Polyethers

The synthesis of medium- and short-chain aliphatic polyethers is industrially limited to the ring-opening polymerization of cyclic ethers with a high ring strain, such as oxiranes, oxetanes, or tetrahydrofuran. This structural limitation can be overcome by the gallium bromide catalyzed reduction of different polyesters into their corresponding polyethers. Herein, the scope of applicable polyesters is broadened, while the influence of the polyester structure on the reduction system is examined. The reactivity as well as side reactions, i.e., overreduction leading to chain cleavage, are shown to depend on the distance of the ester groups in the repeating unit of the polyester. Two different reducing agents, namely triethylsilane and 1,1,3,3-tetramethyldisiloxane, are studied and compared in terms of reactivity and work-up procedures, showing advantages and disadvantages depending on the reduced polyester properties. The reaction conditions are optimized and the reduction can be scaled-up to 60 g polyester. All products are thoroughly characterized

Fully Renewable Non-Isocyanate Polyurethanes via the Lossen Rearrangement

In this work, a straightforward and efficient synthesis approach to renewable non‐isocyanate polyurethanes (NIPUs) is described. For this purpose, suitable and renewable carbamate monomers, possessing two double bonds, are synthesized from hydroxamic fatty acid derivatives via the Lossen rearrangement in a one‐step synthesis, and sustainable dithiols are synthesized from dialkenes derived from renewable feedstock (i.e., limonene and 1,4‐cyclohexadiene). Subsequently, the comonomers are polymerized with the highly efficient thiol–ene reaction to produce NIPUs with M$_{n}$ values up to 26 kg mol$^{−1}$ bearing thioether linkages. The main side product of the Lossen rearrangement, a symmetric urea, can also be polymerized in the same fashion. Important in the view of sustainability, the monomer mixture can also be used directly, without separation. The obtained polymers are characterized by NMR, attenuated total reflection‐infrared spectroscopy, differential scanning calorimetry, and size exclusion chromatography

Olefin cross-metathesis as a valuable tool for the preparation of renewable polyesters and polyamides from unsaturated fatty acid esters and carbamates

Olefin cross-metathesis of unsaturated fatty acid methyl ester (FAME) derived benzyl carbamates with methyl acrylate is described. The obtained by-product{,} an [small alpha]{,}[small beta]-unsaturated ester{,} was further modified via thia-Michael addition reactions in order to synthesize branched AA-type or AB-type monomers for the preparation of polyesters{,} which are tuneable by oxidation. Cross-metathesis of fatty acid derived carbamates was used as a novel approach to prepare linear AB-type monomers{,} which can be used for the preparation of renewable polyamides PA11{,} PA12 and PA15. The necessary fatty acid carbamates were prepared by applying a catalytic Lossen rearrangement procedure. The presented synthesis strategy has potential for the bio-sourced preparation of monomers for the production of polyamides. All prepared polymers were fully characterized by NMR{,} SEC{,} and DSC analyses. Additionally{,} the Young{\u27}s modulus of the prepared long-chain polyamide PA15 was determined

Regeneration of Cellulose from a Switchable Ionic Liquid: Toward More Sustainable Cellulose Fibers

A CO$_{2}$ switchable solvent system is investigated to find an environmentally friendlier way to produce man‐made cellulose fibers. Cellulose solutions with concentrations from 2 wt% to 8 wt%, based on derivative and non‐derivative dissolution approaches, are investigated. Three different switchable solvent systems are tested. After accessing the stability of the produced cellulose solutions, their regeneration is investigated using different alcoholic coagulation media. In order to find a suitable coagulation medium and stable cellulose solution, a dissolution–regeneration cycle is investigated, while trying to minimize the amount of waste by recovering the employed solvents. The process is optimized and the resulting fibers are characterized by infrared (IR) spectroscopy, optical microscopy, as well as scanning electron microscopy

Olefin cross-metathesis as a valuable tool for the preparation of renewable polyesters and polyamides from unsaturated fatty acid esters and carbamates

Olefin cross-metathesis of unsaturated fatty acid methyl ester (FAME) derived benzyl carbamates with methyl acrylate is described. The obtained by-product{,} an [small alpha]{,}[small beta]-unsaturated ester{,} was further modified via thia-Michael addition reactions in order to synthesize branched AA-type or AB-type monomers for the preparation of polyesters{,} which are tuneable by oxidation. Cross-metathesis of fatty acid derived carbamates was used as a novel approach to prepare linear AB-type monomers{,} which can be used for the preparation of renewable polyamides PA11{,} PA12 and PA15. The necessary fatty acid carbamates were prepared by applying a catalytic Lossen rearrangement procedure. The presented synthesis strategy has potential for the bio-sourced preparation of monomers for the production of polyamides. All prepared polymers were fully characterized by NMR{,} SEC{,} and DSC analyses. Additionally{,} the Young{\u27}s modulus of the prepared long-chain polyamide PA15 was determined

RAFT Polymerization of a Renewable Ricinoleic Acid-Derived Monomer and Subsequent Post-Polymerization Modification via the Biginelli-3-Component Reaction

The search for renewable monomers for radical polymerization techniques is of current interest due to the awareness of sustainability requirements in the chemical sciences. Herein, the synthesis and reversible addition-fragmentation chain-transfer (RAFT) polymerization of a renewable methacrylate monomer based on ricinoleic acid as sustainable starting material is presented. In addition, the hydroxy moiety of the ricinoleic acid is converted to an acetoacetate in order to allow for a post-polymerization modification (PPM) using the Biginelli-three-component reaction (B-3CR), rendering the presented monomer a renewable and highly flexible reactant for the synthesis of polymer materials. Consequently, RAFT polymerization yields macromolecules with a molecular weight of up to 15 000 g mo$^{-1}$l and expectedly narrow molecular weight distributions with Ðs around 1.13. The feasibility of chain extension and block copolymer synthesis is demonstrated. Eventually, the PPM of the acetoacetate moiety of the polymer repeating units using the B-3CR is proven to be efficient with conversions of up to 95% of the acetoacetates, while the modification allows for a pronounced increase of the glass transition temperature to approximately room temperature compared to the unmodified polymers (T$_{g}$ = −50 °C)